Field of the invention

The present invention relates to a fucosylated saccharide for use in a method for preventing and/or treating a parasite infection in a subject. More specifically, the present invention relates to a fucosylated saccharide for use in a method for preventing and/or treating cryptosporidiosis.

Background of the invention

Parasites are responsible for a replete amount of diseases among humans and animals, in particular in young or immunocompromised subjects. These parasites are transmitted to their hosts most often through the ingestion of contaminated food or water or through the bite of an antropod. One of the most common parasitic disease found worldwide is cryptosporidiosis. It is a parasitic disease which is caused by Cryptosporidium, a genus of protozoan parasites in the phylum apicomplexa. Cryptosporidiosis is one of the most common waterborne diseases and can also be transmitted to humans and other animals including cattle, pigs, sheep, horses and goats among others. Cryptosporidiosis generally affects the distal small intestine, but can also affect the respiratory tract in both immunocompetent and immunocompromised subjects. It is most commonly caused by the parasites Cryptosporidium parvum and Cryptosporidium hominis. Several species of Cryptosporidium can infect a range of farmed animals, i.e. animals that are reared in an agricultural setting in order to produce various commodities such as food (meat, organs, eggs, dairy products) and/or hair or wool and hence impose a major veterinary concern. Due to the zoonotic nature of several of these Cryptosporidium species, the public health may also be affected by Cryptosporidium infections in farmed animals. It is specifically referred to table 4.1 of Robertson et al, 2014, which is incorporated by reference in its entirety, which provides an overview of Cryptosporidium species infecting farmed animals. Besides farmed animals, horses, birds and fish can also be infected, in addition to dogs and cats (Caccio and Widmer, 2014; incorporated by reference).

Parasitic disease, and in particular cryptosporidiosis, represents a significant disease in both humans and animals worldwide. At present, there are no vaccines available and there are only a few treatment options in either humans or animals. Nitazoxanide is indicated for use in immunocompetent humans and represent the current standard of care albeit that its efficacy is low, especially in young children, and barely different from placebo in for example HIV patients, whereas Halocure® is for use in new-born calves. Available treatments for cryptosporidiosis are very limited with no consistently effective treatment and often with a high incidence of undesirable side effects which often leads to use being contraindicated in certain circumstances.

The development of an effective therapeutic for preventing and/or treating parasitic disease such as cryptosporidiosis, is a medical and public health imperative.

Summary of the invention

It was surprisingly found that a fucosylated saccharide according to the invention proves to be an efficacious agent to prevent and/or treat a parasite infection, in particular cryptosporidiosis. Said fucosylated saccharide is not associated with adverse effects and is safe to use in humans and animals even while pregnant and/or lactating.

In a first aspect, the invention provides a saccharide comprising a fucose (i.e. fucosylated saccharide) for use in a method for preventing and/or treating a parasite infection in a subject.

In a second aspect, the invention provides a composition comprising a fucosylated saccharide for use in a method for preventing and/or treating a parasite infection in a subject.

In a third aspect, the invention provides a method for preventing and/or treating a parasite infection in a subject, wherein a fucosylated saccharide or a composition comprising a fucosylated saccharide is administered to a subject.

In a fourth aspect, the invention provides the use of a fucosylated saccharide or composition comprising a fucosylated saccharide for the manufacture of a medicament for preventing and/or treating a parasite infection in a subject.

Detailed description of the invention

Saccharide for use in preventing/treating a parasite infection

In a first aspect, the invention provides a saccharide comprising a fucose for use in a method for preventing and/or treating a parasite infection in a subject.

In the context of the present invention, the term "preventing" a parasite infection or a disease such as cryptosporidiosis as described herein, preferably means avoiding that said parasite infection or disease occurs and/or decreasing the incidence of said infection or disease. In other words, "preventing" preferably refers to ameliorating the risk of suffering from said parasite infection or said disease. The term "prevention" and "prophylaxis" are interchangeably used in the context of the present invention. The term "treating" a parasite infection or a disease such as cryptosporidiosis as described herein, preferably means inhibiting said infection or disease, e.g. arresting the development of said infection or disease; relieving said infection or disease, for example causing regression of said infection or disease; and/or relieving a condition caused by or resulting from said infection or disease, e.g. relieving, preventing or treating symptoms of said infection or disease. In other words, "treating" preferably refers to decreasing the duration (number of days/weeks/months/years) the subject will suffer from said infection or disease), the risks, the complications and/or the severity of said infection or disease; this also encompasses the relief of the symptoms caused by said infection or disease.

Saccharide

In an embodiment of the first aspect of the invention, said saccharide comprises a fucose. Preferably, said saccharide comprises only one fucose, i.e. said saccharide comprises one or more monosaccharides and only one of said monosaccharides is a fucose. As understood by the skilled person, the term "saccharide" refers to a molecule comprising at least one monosaccharide, i.e. a saccharide is a molecule consisting of one or more monosaccharide residue(s). The term "monosaccharide" as used herein refers to a sugar that is not decomposable into simpler sugars by hydrolysis, is classed either an aldose or ketose, and contains one or more hydroxyl groups per molecule. Monosaccharides are saccharides containing only one simple sugar.

In an additional and/or alternative embodiment, said saccharide is a neutral saccharide. A "neutral" saccharide as used herein and as generally understood in the state of the art is a saccharide that has no negative charge originating from a carboxylic acid group.

In an additional and/or alternative embodiment, said fucose of a saccharide according to the invention is linked to a monosaccharide in an alpha-1,2-, alpha-1,3- or alpha-1, 4-linkage, preferably an alpha-1,2- or an alpha-1, 3-linkage, more preferably an alpha-1, 2-linkage, and wherein said monosaccharide is preferably selected from glucose, N-acetylglucosamine and galactose, more preferably said monosaccharide is glucose or galactose, even more preferably said monosaccharide is galactose. The skilled person will understand that the expression "fucose is linked to a monosaccharide" refers to the situation wherein the fucose is bound to a monosaccharide through a glycosidic bond and wherein said fucose and monosaccharide are part of the saccharide of the invention (which can comprise additional monosaccharide(s) than said fucose and said monosaccharide unless said saccharide is a disaccharide).

In a preferred embodiment, said saccharide is a disaccharide or an oligosaccharide. In a more preferred embodiment, said saccharide is an oligosaccharide. In the context of the present invention, the term "oligosaccharide" preferably refers to a saccharide containing 2 up to and including 20 monosaccharides, i.e. the degree of polymerization (DP) is 2-20. An oligosaccharide can be a linear structure or can include branches. The linkage (e.g. glycosidic linkage, galactosidic linkage, glucosidic linkage, etc.) between two sugar units can be expressed, for example, as 1,4, l->4, or (1-4), used interchangeably herein. Each monosaccharide can be in the cyclic form (e.g. pyranose or furanose form). An oligosaccharide can contain both alpha- and beta-glycosidic bonds or can contain only beta-glycosidic bonds.

More preferably, said oligosaccharide consists of 3-9, preferably 3-8, more preferably 3-7, even more preferably 3-6, even more preferably 3-5, monosaccharides.

In an additional and/or alternative preferred embodiment, said saccharide according to the invention is a mammalian milk oligosaccharide (MMO), preferably a human milk oligosaccharide (HMO). Mammalian milk oligosaccharides (MMOs) comprise oligosaccharides present in milk found in any phase during lactation including colostrum milk from humans (i.e. human milk oligosaccharides or HMOs) and mammals including but not limited to cows (Bos Taurus), sheep (Ovis aries), goats (Capra aegagrus hircus), bactrian camels (Camelus bactrianus), horses (Eguus ferus caballus), pigs (Sus scropha), dogs (Canis lupus familiaris), ezo brown bears (Ursus arctos yesoensis), polar bear (Ursus maritimus), Japanese black bears (Ursus thibetanus japonicus), striped skunks (Mephitis mephitis), hooded seals (Cystophora cristata), Asian elephants (Elephas maximus), African elephant (Loxodonta africana), giant anteater (Myrmecophaga tridactyla), common bottlenose dolphins (Tursiops truncates), northern minke whales (Balaenoptera acutorostrata), tammar wallabies (Macropus eugenii), red kangaroos (Macropus rufus), common brushtail possum (Trichosurus Vulpecula), koalas (Phascolarctos cinereus), eastern quolls (Dasyurus viverrinus), platypus (Ornithorhynchus anatinus). Human milk oligosaccharides (HMOs) are also known as human identical milk oligosaccharides which are chemically identical to the human milk oligosaccharides found in human breast milk but which are biotechnologically-produced (e.g. using cell free systems or cells and organisms comprising a bacterium, a fungus, a yeast, a plant, animal, or protozoan cell, preferably genetically engineered cells and organisms). Human identical milk oligosaccharides are marketed under the name HiMO.

In an additional and/or alternative preferred embodiment, said saccharide according to the invention comprises a lactose, a lacto-N-biose (LNB) or N-acetyllactosamine (LacNAc) at its reducing end, preferably said saccharide according to the invention comprises a lactose at is reducing end.

In an additional and/or alternative preferred embodiment, said saccharide according to the invention is selected from a list consisting of 2'-fucosyllactose (2'FL), 3-fucosyllactose (3-FL), difucosyllactose (diFL), 2'-fucosyl-N-acetyllactosamine (2'FlacNAc), difucosyl-N-acetyllactosamine (diFLacNAc), 3-fucosyl-N- acetyllactosamine (3FlacNAc), 2'-fucosyllacto-N-biose (2'FLNB), 4-fucosyllacto-N-biose (4FLNB), difucosyllacto-N-biose (diFLNB), lacto-N-fucopentaose I (LNFP I), blood group A antigen hexaose type 1 (GalNAc-LNFP I), blood group B antigen hexaose type 1 (Gal-LNFP I), lacto-N-fucopentaose II (LNFP II), lacto-N-fucopentaose III (LNFP III), lacto-N-fucopentaose V (LNFP V), lacto-N-difucohexaose I (LNDFH I), lacto-N-difucohexaose II (LNDFH II), lewis b-lewis x, monofucosyllacto-N-hexaose III (MFLNH III), difucosyllacto-N-hexaose (a) (DFLNH (a)), difucosyllacto-N-hexaose (DFLNH), trifucosyllacto-N-hexaose (TFLNH), lacto-N-neofucopentaose I (LNnFP I), lacto-N-neofucopentaose V (LNnFP V, LNFP VI), and lacto- N-neodifucohexaose (LNnDFH). Said saccharides are commercially available and/or the production/purification of any of said saccharides has been described and allows the skilled person to produce/obtain any of said saccharides accordingly. An exemplary reference is provided for each saccharide and each reference is incorporated by reference:

- 2'FL: Zhou et al, 2021; Lu et al, 2021 ; W02022/034073; Carbosynth (OF06739)

- 3-FL: Zhou et al, 2021; Lu et al, 2021 ; W02022/034073; Carbosynth (OF05673)

- di FL: W02022/034073

- 2'FlacNAc: WO 2022/034075

- 3FlacNAc: WO 2022/034075

- diFLacNAc: WO 2022/034075

- 2'FLNB: WO 2022/034075

- 4FLNB: WO 2022/034075

- diFLNB: WO 2022/034075

- LNFP I: Derya et al, 2020 ; Carbosynth (OL05676)

- GalNAc-LNFP I: WO 2022/034077

- Gal-LNFP I: WO 2022/034077

- LNFP II: Zeuner et al, 2018

- LNFP III: Zeuner et al, 2018 ; Carbosynth (OL04212)

- LNFP V: W02020/115671; Carbosynth (OL06817)

- LNDFH I: Huang et al, 2021; Carbosynth (OL01664)

- LNDFH II: Yu et al, 2017 ; Huang et al, 2021 ; Carbosynth (OL06826)

- MFLNH III: Carbosynth (OM05898)

- DFLNH (a): Carbosynth (OD05375)

- DFLNH: Carbosynth (OD06532)

- TFLNH: Isosep (57/18-0010)

- LNnFP I: Elicityl (GLY033-2-90%)

LNnFP V: Dumon et al, 2001

LNnDFH: Dumon et al, 2001

In an additional and/or alternative preferred embodiment, said saccharide according to the invention is selected from a list consisting of 2'FL, diFL, LNFP I, GalNAc-LNFP I, Gal-LNFP I, LNDFH I, lewis b-lewis x, DFLNH (a), TFLNH, 2'FLNB, diFLNB, 2'FlacNAc and diFLacNAc, preferably selected from a list consisting of 2'FL, diFL, LNFP I, 2'FLNB, diFLNB, 2'FlacNAc and diFLacNAc, more preferably selected from a list consisting of 2'FL, diFL, 2'FLNB, diFLNB, 2'FlacNAc and diFLacNAc, even more preferably selected from a list consisting of 2'FL, 2'FLNB and 2'FlacNAc, even more preferably wherein said saccharide is 2'FL or diFL, most preferably wherein said saccharide is 2'FL.

In another embodiment, said saccharide of the invention has been isolated from a microbial cultivation or fermentation, cell culture, enzymatic reaction or chemical reaction. Alternatively, said saccharide of the invention has been isolated by e.g. chromatography or filtration technology from a natural source such as a human or animal milk, preferably animal milk. For example Zhou et al, 2021, provides a review on methods (e.g. enzymatic and microbial production) used for the production of 2'-fucosyllactose, an exemplary saccharide according to the invention, and which is incorporated in its entirety herein.

In a preferred embodiment, said saccharide of the invention has been produced, preferably in vitro and/or ex vivo, by a cell, preferably a single cell, wherein said cell is preferably chosen from the list consisting of a microorganism, a plant cell, an animal cell or a protozoan cell. In other words, said saccharide of the invention has been produced by an in vitro and/or ex vivo culture of cells, wherein said cells are preferably chosen from the list consisting of a microorganism, a plant cell, an animal cell or a protozoan cell.

Preferably, said cell is a microorganism. Preferably, said microorganism is selected from a list consisting of a bacterium, a yeast or a fungus. Further, it is preferred that said cell is genetically engineered for the production of said saccharide according to the invention. Throughout the description and claims, the terms "has been isolated" and "is obtained" are interchangeably used, unless specifically stated otherwise.

The latter bacterium preferably belongs to the phylum of the Proteobacteria or the phylum of the Firmicutes or the phylum of the Cyanobacteria or the phylum Deinococcus-Thermus, preferably belongs to the phylum of the Proteobacteria. The latter bacterium belonging to the phylum Proteobacteria belongs preferably to the family Enterobacteriaceae, preferably to the species Escherichia coli. The latter bacterium preferably relates to any strain belonging to the species Escherichia coli such as but not limited to Escherichia coli B, Escherichia coli C, Escherichia coli W, Escherichia coli K12, Escherichia coli Nissle. More specifically, the latter term relates to cultivated Escherichia coli strains - designated as E. coli K12 strains - which are well-adapted to the laboratory environment, and, unlike wild type strains, have lost their ability to thrive in the intestine. Well-known examples of the E. coli K12 strains are K12 Wild type, W3110, MG1655, M182, MC1000, MC1060, MC1061, MC4100, JM101, NZN111 and AA200. Hence, preferably the present invention specifically relates to a mutated and/or transformed Escherichia coli strain as indicated above wherein said E. coli strain is a K12 strain. More specifically, the present invention relates to a mutated and/or transformed Escherichia coli strain as indicated above wherein said K12 strain is E. coli MG1655. The latter bacterium belonging to the phylum Firmicutes belongs preferably to the Bacilli, preferably from the species Bacillus, such as Bacillus subtilis or, B. amyloliquefaciens. The latter Bacterium belonging to the phylum Actinobacteria, preferably belonging to the family of the Corynebacteriaceae, with members Corynebacterium glutamicum or C. afermentans, or belonging to the family of the Streptomycetaceae with members Streptomyces griseus or S. fradiae. The latter yeast preferably belongs to the phylum of the Ascomycota or the phylum of the Basidiomycota or the phylum of the Deuteromycota or the phylum of the Zygomycetes. The latter yeast belongs preferably to the genus Saccharomyces (with members like e.g. Saccharomyces cerevisiae, S. bayanus, S. boulardii), Pichia (with members like e.g. Pichia pastoris, P. anomala, P. kluyveri), Komagataella, Hansunella, Kluyveromyces (with members like e.g. Kluyveromyces lactis, K. marxianus, K. thermotolerans), Yarrowia (like e.g. Yarrowia lipolytica), Eremothecium, Zygosaccharomyces, Starmerella l ike e.g. Starmerella bombicola) or Debaromyces. The latter yeast is preferably selected from Pichia pastoris, Yarrowia lipolitica, Saccharomyces cerevisiae and Kluyveromyces lactis. The latter fungus belongs preferably to the genus Rhizopus, Dictyostelium, Penicillium, Mucor or Aspergillus. "Plant cells" includes cells of flowering and nonflowering plants, as well as algal cells, for example Chlamydomonas, Chlorella, etc. Preferably, said plant cell is a tobacco, alfalfa, rice, cotton, rapeseed, tomato, corn, maize or soybean cell. The latter animal cell is preferably derived from non-human mammals (e.g. cattle, buffalo, pig, sheep, mouse, rat), birds (e.g. chicken, duck, ostrich, turkey, pheasant), fish (e.g. swordfish, salmon, tuna, sea bass, trout, catfish), invertebrates (e.g. lobster, crab, shrimp, clams, oyster, mussel, sea urchin), reptiles (e.g. snake, alligator, turtle), amphibians (e.g. frogs) or insects (e.g. fly, nematode) or is a genetically modified cell line derived from human cells excluding embryonic stem cells. Both human and non-human mammalian cells are preferably chosen from the list comprising an epithelial cell like e.g. a mammary epithelial cell, mammary myoepithelial cell, mammary progenitor cell, an embryonic kidney cell (e.g. HEK293 or HEK 293T cell), a fibroblast cell, a COS cell, a Chinese hamster ovary (CHO) cell, a murine myeloma cell like e.g. an 1X120, SP2/0 or YB2/0 cell, an NIH-3T3 cell, a non-mammary adult stem cell or derivatives thereof such as described in WO21067641, preferably mesenchymal stem cell or derivates thereof as described in WO21067641. Said insect cell is preferably derived from Spodoptera frugiperda like e.g. Sf9 or Sf21 cells, Bombyx mori, Mamestra brassicae, Trichoplusia ni like e.g. BTI-TN-5B1-4 cells or Drosophila melanogaster like e.g. Drosophila S2 cells. The latter protozoan cell preferably is a Leishmania tarentolae cell.

In an additional and/or alternative preferred embodiment, said saccharide of the invention has been produced, preferably in vitro and/or ex vivo, by a mammary epithelial cell, mammary myoepithelial cell and/or mammary progenitor cell, preferably wherein said cell is generated from non-mammary adult stem cells, more preferably wherein said cell is generated from mesenchymal stem cells. Such cells are well-known to the skilled person, it is in this regard referred to for example WO2021/067641 and WO2021/242866 (mammary epithelial cells derived from non-mammary adult stem cells, preferably from mesenchymal stem cells) and WO2021/142241 (mammary epithelial cells, mammary myoepithelial cells, mammary progenitor cells).

In another additional and/or alternative preferred embodiment, said saccharide of the invention has been produced, preferably in vitro and/or ex vivo, by a microorganism cell, preferably said microorganism is a bacterium, a yeast or a fungus, more preferably said microorganism is a bacterium or a yeast, even more preferably said microorganism is a bacterium, most preferably said microorganism is Escherichia coli. In the context of the invention, it is also within the scope of the present invention that two or more different cells (preferably as defined herein), produce the saccharide according to the invention. It is however preferred that a single cell produces said saccharide, i.e. a single culture of said cell produces the saccharide of the invention.

In an additional and/or alternative preferred embodiment, said saccharide according to the invention is typically isolated from a microbial cultivation or fermentation, cell culture, enzymatic reaction or chemical reaction as described herein, resulting in a solution containing said saccharide. Such a solution can for example be obtained by a method comprising the steps of:

(a) cultivating at least one cell as defined herein, preferably a single cell, that is capable to produce said saccharide in a suitable cultivation medium to form a cultivation broth, preferably wherein said cell is metabolically engineered for the production of said saccharide or said mixture, and

(b) purifying said saccharide from the cultivation broth by:

(i) clarifying the cultivation broth, and

(ii) removing salts and/or medium components form said clarified cultivation broth, and/or

(iii) concentrating said saccharide in said clarified cultivation broth, thereby providing a solution comprising a purified saccharide.

In the context of the invention, "clarifying the cultivation broth" refers to the removal of suspended particulates and contaminants, particularly cells, cell components, insoluble metabolites and debris produced by culturing the cell according to the invention. Clarification is preferably one or more of centrifugation, flocculation, decantation and/or filtration.

In the context of the invention, "removing salts and/or medium components form said clarified cultivation broth" refers to removing substantially all the proteins, as well as peptides, amino acids, RNA and DNA and any endotoxins and glycolipids from said clarified cultivation broth, preferably after it has been. In this step, proteins and related impurities can be removed from said saccharide in a conventional manner. Preferably, proteins, salts, by-products, colour, endotoxins and other related impurities are removed from said saccharide by ultrafiltration, nanofiltration, two-phase partitioning, reverse osmosis, microfiltration, activated charcoal or carbon treatment, treatment with non-ionic surfactants, enzymatic digestion, tangential flow high-performance filtration, tangential flow ultrafiltration, electrophoresis (e.g. using slabpolyacrylamide or sodium dodecyl sulphate-polyacrylamide gel electrophoresis (PAGE)), affinity chromatography (using affinity ligands including e.g. DEAE-Sepharose, poly-L-lysine and polymyxin-B, endotoxin-selective adsorber matrices), ion exchange chromatography (such as but not limited to cation exchange, anion exchange, mixed bed ion exchange, inside-out ligand attachment), hydrophobic interaction chromatography and/or gel filtration (i.e., size exclusion chromatography), particularly by chromatography, more particularly by ion exchange chromatography or hydrophobic interaction chromatography or ligand exchange chromatography. With the exception of size exclusion chromatography, proteins and related impurities are retained by a chromatography medium or a selected membrane, said saccharide remains in the said saccharide containing clarified cultivation broth.

Further purification of said saccharide may be accomplished, for example, by use of (activated) charcoal or carbon, nanofiltration, ultrafiltration, electrophoresis, enzymatic treatment or ion exchange to remove any remaining DNA, protein, LPS, endotoxins, or other impurity. Alcohols, such as ethanol, and aqueous alcohol mixtures can also be used. Another purification step is accomplished by crystallization, evaporation or precipitation of the product.

Several drying techniques are known to the skilled person which can be used to obtain powder from a solution containing said saccharide. Powder is preferably obtained by spray drying, freeze drying, spray freeze-drying, crystallization, lyophilization, band or belt drying, drum or roller drying, and/or agitated thin film drying, preferably by spray drying, drum or roller drying, or agitated thin film drying, more preferably by spray drying or agitated thin film drying, most preferably by spray drying, of a solution containing said saccharide. Preferably, said saccharide according to the invention constitutes > 70.0 %, preferably > 75.0 %, more preferably > 80.0, (w/w) of said powder. Preferably, said powder contains < 15 wt. %, preferably < 10 wt. %, more preferably < 9 wt. %, more preferably < 8 wt. %, more preferably < 7 wt. %, even more preferably < 5 wt. %, even more preferably < 4 wt. % of liquid, even more preferably < 3 wt. % of liquid, even more preferably < 2 wt. % of liquid, most preferably < 1 wt. %, preferably wherein said liquid is water.

In an additional and/or alternative embodiment, said saccharide according to the invention is linked, preferably chemically linked, to a carrier for delivery of said saccharide. Preferably, said carrier is a ceramide-based carrier or a polypeptide-based carrier, more preferably said carrier is a ceramide-based carrier. Preferably, said polypeptide-based carrier is epsilon-polylysine, alfa-polylysine, poly(aspartic acid), polyglutamic acid or polyornithine. These carriers are commercially available (e.g. Sigma-Aldrich, Carbosynth). Said ceramide-based carrier is preferably selected from a list consisting of dl8:l/16:0, tl8:0- 16:0, tl8:0-hl6:0, tl8:0-h22:0 and tl8:0-h24:0. These ceramide carriers are commercially available and well-known to the skilled person and are for example described in W02010/037785 which is incorporated by reference. dl8:l/16:0 is also known as C16 ceramide and N-palmitoylsphingosine and therefore interchangeable used herein. tl8:0-16:0 is also known as C16 phytoceramide and N-hexadecanoyl phytosphingosine and therefore interchangeable used herein. tl8:0-hl6:0, tl8:0-h22:0 and tl8:0-h24:0 are glycosylinositolphosphoceramides (GIPCs). As known to the skilled person, "d" and "t" refer to the hydroxylation state of the whole ceramide or long-chain base moiety (d is 2 groups, t is 3 groups), whereas "h" denotes a hydroxylation of the fatty acyl group. Parasite infection

In an embodiment of the first aspect of the invention, said saccharide comprising a fucose is for use in a method for preventing and/or treating a parasite infection in a subject. Preferably, said parasite is a singlecelled parasite, more preferably said parasite is a single-celled protozoan.

In preferred embodiment, said parasite is a Cryptosporidium species, preferably wherein said parasite is selected from a list consisting of Cryptosporidium parvum, Cryptosporidium suis, Cryptosporidium scrofarum, Cryptosporidium hominis, Cryptosporidium bovis, Cryptosporidium andersoni, Cryptosporidium ruyanae, Cryptosporidium felis, Cryptosporidium canis, Cryptosporidium meleagridis, Cryptosporidium baileyi, Cryptosporidium cuniculus, Cryptosporidium xiaoi, Cryptosporidium ubiquitum, Cryptosporidium viatorum, Cryptosporidium muris, Cryptosporidium molnari, Cryptosporidium scophthalmi, Cryptosporidium huw, Cryptosporidium serpentis and Cryptosporidium varanii. More preferably wherein said parasite is selected from a list consisting of Cryptosporidium parvum, Cryptosporidium suis, Cryptosporidium scrofarum, Cryptosporidium hominis, Cryptosporidium bovis, Cryptosporidium andersoni, Cryptosporidium galli and Cryptosporidium ruyanae, even more preferably wherein said parasite is selected from a list consisting of Cryptosporidium parvum, Cryptosporidium suis and Cryptosporidium scrofarum, most preferably wherein said parasite is Cryptosporidium parvum. Throughout the application and claims, unless specifically stated otherwise, the term "Cryptosporidium species" is preferably replaced with "Cryptosporidium sp." or "Cryptosporidium spp." and vice versa.

In an additional and/or alternative preferred embodiment, said parasite is a Cryptosporidium species which is able to infect at least one subject as described in the section "subject".

In an additional and/or alternative preferred embodiment, said parasite is a Cryptosporidium species which is able to infect a farmed animal. Preferably, said farmed animal is selected from a list consisting of a pig, bovine, horse, sheep, goat, camelid, rabbit and poultry. More preferably, said farmed animal is a pig, bovine or horse. Even more preferably, said farmed animal is a pig or bovine. Most preferably, said farmed animal is a pig. Robertson et al, 2014 describes cryptosporidiosis in farmed animals and provides an overview of different farmed animals and the Cryptosporidium species known to be able to infect these different farmed animals (it is referred to Table 4.1 of Robertson et al, 2014 which is incorporated by reference). More preferably said parasite is a Cryptosporidium species selected from a list consisting of: subject is a pig: Cryptosporidium parvum, Cryptosporidium suis and Cryptosporidium scrofarum; subject is bovine: Cryptosporidium parvum, Cryptosporidium bovis, Cryptosporidium andersoni and Cryptosporidium ruyanae; subject is a horse: Cryptosporidium parvum, Cryptosporidium hominis, Cryptosporidium muris and Cryptosporidium andersoni; subject is a sheep: Cryptosporidium parvum, Cryptosporidium xiaoi and Cryptosporidium ubiquitum; subject is a goat: Cryptosporidium parvum, Cryptosporidium xiaoi and Cryptosporidium ubiquitum; subject is a camelid: Cryptosporidium parvum; subject is a rabbit: Cryptosporidium cuniculus; subject is poultry: Cryptosporidium meleagridis and Cryptosporidium baileyi.

In an additional and/or alternative preferred embodiment, said parasite is a Cryptosporidium species which is able to infect a human. Preferably, said parasite is selected from a list consisting of Cryptosporidium parvum, Cryptosporidium hominis, Cryptosporidium meleagridis, Cryptosporidium viatorum, Cryptosporidum felis, Cryptosporidium canis and Cryptosporidium muris. More preferably, said parasite is selected from a list consisting of Cryptosporidium parvum, Cryptosporidium hominis, Cryptosporidium meleagridis and Cryptosporidium viatorum. Even more preferably, said parasite is selected from a list consisting of Cryptosporidium parvum, Cryptosporidium hominis and Cryptosporidium meleagridis. Even more preferably, said parasite is Cryptosporidium parvum or Cryptosporidium hominis. Most preferably, said parasite is Cryptosporidium parvum.

In an additional and/or alternative preferred embodiment, said parasite is a Cryptosporidium species which is able to infect a horse. Preferably, said parasite is selected from a list consisting of Cryptosporidium parvum, Cryptosporidium hominis, Cryptosporidium muris and Cryptosporidium andersoni.

In an additional and/or alternative preferred embodiment, said parasite is a Cryptosporidium species which is able to infect a companion animal, preferably wherein said companion animal is a dog or a cat. If said subject is a cat, then said parasite is preferably Cryptosporidium parvum or Cryptosporidium felis, more preferably Cryptosporidium felis. If said subject is a dog, then said parasite is preferably Cryptosporidium parvum or Cryptosporidium canis, more preferably Cryptosporidium canis.

In an additional and/or alternative preferred embodiment, said parasite is a Cryptosporidium species which is able to infect a bird. Preferably, said parasite is selected from a list consisting of Cryptosporidium baileyi, Cryptosporidium meleagridis and Cryptosporidium galli. More preferably, said parasite is Cryptosporidium baileyi or Cryptosporidium meleagridis.

In an additional and/or alternative preferred embodiment, said parasite is a Cryptosporidium species which is able to infect a fish. Preferably, said parasite is selected from a list consisting of Cryptosporidium molnari, Cryptosporidium scophthalmi, Cryptosporidium huw, Cryptosporidium parvum, Cryptosporidium hominis, Cryptosporidium scrofarum and Cryptosporidium xiaoi. More preferably, said parasite is selected from a list consisting of Cryptosporidium molnari, Cryptosporidium scophthalmi and Cryptosporidium huw.

In an additional and/or alternative preferred embodiment, said parasite is a Cryptosporidium species which is able to infect a reptile. Preferably, said parasite is selected from a list consisting of Cryptosporidium serpentis, Cryptosporidium varanii, Cryptosporidium parvum and Cryptosporidium muris. More preferably, said parasite is Cryptosporidium serpentis or Cryptosporidium varanii.

In an additional and/or alternative preferred embodiment, said saccharide comprising a fucose is for use in a method for preventing and/or treating cryptosporidiosis. The latter is a parasitic disease caused by a Cryptosporidium species, preferably as described herein. Throughout the application, unless specifically stated otherwise, "for use in a method for preventing and/or treating a parasite infection" is preferably replaced with "for use in a method for preventing and/or treating cryptosporidiosis".

In an embodiment of the first aspect of the invention, said saccharide comprising a fucose is for use in a method for preventing and/or treating a parasite infection in a subject. Preferably, said subject is a human or an animal, more preferably said subject is an animal. Throughout the description and claims, unless specifically stated otherwise, the term "subject" can be preferably replaced with "subject in the need thereof".

Preferably, said animal is selected from a list consisting of a farmed animal, a horse, a companion animal, a bird, a fish and a reptile, more preferably wherein said animal is a farmed animal, even more preferably wherein said animal is a farmed animal selected from a list consisting of pig, bovine, horse, sheep, goat, camelid, rabbit and poultry, even more preferably wherein said animal is a pig, bovine or horse, even more preferably wherein said animal is a pig or bovine, most preferably wherein said animal is a pig.

As understood by the skilled person, a "farmed animal" refers to an animal that is reared in an agricultural setting in order to produce various commodities such as food (meat, organs, eggs, dairy products) and/or hair or wool. Further, a "companion animal" preferably refers to a domestic animal.

In a preferred embodiment, said subject is an adult or a non-adult subject, preferably said subject is a non-adult subject.

In an additional and/or alternative preferred embodiment, said subject is a non-adult human, preferably an infant (age of 0-1 year) or a child of 1-9 years, more preferably an infant (age of 0-1 year) or a child of 1-6 years, even more preferably an infant (age of 0-1 year) or a child of 1-4 years.

In an additional and/or alternative preferred embodiment, said subject is a non-adult animal, preferably selected from a list consisting of piglet, calf, foal, lamb, kid, cria, kitten, chick and puppy, more preferably selected from a list consisting of piglet, calf, foal, lamb, kid, cria, kitten and chick, even more preferably a piglet, calf or foal, even more preferably a piglet or calf, most preferably a piglet. As the skilled person understands, a non-adult animal of a pig, bovine, horse, sheep, goat, camelid, rabbit, poultry, dog, cat (as described earlier herein) is called a piglet, calf, foal, lamb, kid, cria, kitten, chick, puppy, kitten, respectively. Throughout the application, unless specifically stated otherwise, a "non-adult animal" can be replaced with "juvenile animal" and vice versa.

Method for preventing and/or treating

In an embodiment of the first aspect of the invention, a saccharide according to the invention is for use in a method for preventing and/or treating a parasite infection in a subject. In an additional and/or alternative embodiment, a saccharide according to the invention is for use in a method for preventing and/or treating cryptosporidiosis.

In a preferred embodiment, said method according to the invention comprises administering an effective amount of said saccharide according to the invention to said subject. As understood by the skilled person, an "effective amount" is the amount of said saccharide which is required to confer a therapeutic effect on the subject as described in the present application. Effective amounts vary, as recognized by those skilled in the art, depending on the subject, route of administration, excipient usage among other known factors.

In an additional and/or alternative embodiment, said saccharide according to the invention is administered at a daily dose of 0.01-150.0 mg, preferably 0.01-125.0 mg, more preferably 0.01-100.0 mg, even more preferably 0.01-80.0 mg, per kg bodyweight of said subject. In the context of the present invention, an amount of a saccharide according to the invention expressed in a number of grams or milligrams per daily dose as used herein means that the amount of the saccharide is such that when administering the daily dosage to a subject, the subject will be administered with the number of grams or milligrams of the saccharide. In other words, if the daily dosage is for example 50 mg, then the subject receives in total 50 mg per day. This may be in one or more portions. So, if the daily dosage is 50 mg divided over 2 portions, then a single serving consists of 25 mg, a daily serving consists of 2 of such single servings.

In an additional and/or alternative embodiment, said saccharide according to the invention is administered at a daily dose of 1.0-150.0 mg, preferably 1.0-125.0 mg, more preferably 5.0-125.0 mg, even more preferably 10.0-125.0 mg, even more preferably 10.0-100.0 mg, even more preferably 10.0- 80.0 mg, even more preferably 15.0-80.0 mg, even more preferably 20.0-80.0 mg, even more preferably 25.0-80.0 mg, even more preferably 30.0-80.0 mg, even more preferably 35.0-80.0 mg, even more preferably 40.0-80.0 mg, most preferably 45.0-80.0 mg, per kg bodyweight of said subject. This is for example particularly preferred if said subject is a pig, preferably a piglet.

In an additional and/or alternative embodiment, said saccharide according to the invention is administered at daily dose of 0.01-50.0 mg, preferably 0.01-30.0 mg, more preferably 0.01-25.0 mg, even more preferably 0.01-20.0 mg, even more preferably 0.01-15.0 mg, even more preferably 0.01-10.0 mg, even more preferably 0.05-10.0 mg, most preferably 0.1-10.0 mg, per kg bodyweight of said subject. This is for example particularly preferred if said subject is bovine, preferably a non-adult bovine.

In an additional and/or alternative embodiment, said saccharide according to the invention is administered at a daily dose of 0.01-15.0 g, preferably 0.01-10.0 g, more preferably 0.01-5.0 g, even more preferably 0.01-2.0 g, even more preferably 0.01-1.0 g, even more preferably 0.015-1.0 g, most preferably 0.02-1.0 g.

In an additional and/or alternative embodiment, said saccharide according to the invention is administered at a daily dose of 0.01-5.0 g, preferably 0.1-2.5 g, more preferably 0.1-1.5 g, even more preferably 0.1-1.2 g, even more preferably 0.2-1.2 g, even more preferably 0.3-1.2 g, even more preferably 0.4-1.2 g, most preferably 0.5-1.2 g. This is for example particularly preferred if said subject is a pig, preferably a piglet.

In an additional and/or alternative embodiment, said saccharide according to the invention is administered at daily dose of 0.01-1.0 g, preferably 0.01-0.75 g, more preferably 0.01-0.65 g, even more preferably 0.01-0.60 g, even more preferably 0.01-0.50 g, even more preferably 0.015-0.50 g, even more preferably 0.015-0.40 g, even more preferably 0.015-0.30 g, most preferably 0.015-0.20 g. This is for example particularly preferred if said subject is bovine, preferably a non-adult bovine.

In a more preferred embodiment, said saccharide according to the invention is administered to said subject at least once between birth (0 weeks) and 5 weeks of age, preferably between birth and 4 weeks of age, more preferably between birth and 3 weeks of age.

In an additional and/or alternative more preferred embodiment, said saccharide according to the invention is administered to said subject for 1-30, preferably 1-25, more preferably 1-20, even more preferably 1-15, even more preferably 1-10, even more preferably 1-7.5, even more preferably 1-5, even more preferably 1-4, most preferably 1-3, consecutive weeks. Preferably, said saccharide according to the invention is administered at least once a week (i.e. at least one daily dosage is administered in a week), more preferably at least once every 3 days, even more preferably at least once every 2 days, most preferably at least once daily (i.e. a daily dosage is administered every day).

In an additional and/or alternative more preferred embodiment, said saccharide according to the invention is administered to said subject for: if subject is a pig: 1-5, preferably 1-4, more preferably 1-3, most preferably 2-3, consecutive weeks; if subject is bovine: 1-36, preferably 1-32, more preferably 1-30, even more preferably 1-28, even more preferably 1-26, even more preferably 1-18, even more preferably 1-12, even more preferably 1-6, most preferably 1-4, consecutive weeks;

If subject is a dog: 1-5, preferably 1-4, more preferably 1-3, most preferably 2-3, consecutive weeks;

If subject is a cat: 1-5, preferably 1-4, more preferably 1-3, most preferably 2-3, consecutive weeks; if subject is a horse: 1-12, preferably 1-8, more preferably 1-5, even more preferably 1-3, most preferably 1-2, consecutive weeks; if subject is a sheep: 1-36, preferably 1-32, more preferably 1-30, even more preferably 1-28, even more preferably 1-26, even more preferably 1-18, even more preferably 1-12, even more preferably 1-6, most preferably 1-4, consecutive weeks; if subject is a goat: 1-36, preferably 1-32, more preferably 1-30, even more preferably 1-28, even more preferably 1-26, even more preferably 1-18, even more preferably 1-12, even more preferably 1-6, most preferably 1-4, consecutive weeks; if subject is a camelid: 1-12, preferably 1-10, more preferably 1-8, even more preferably 1-6, even more preferably 1-5, even more preferably 1-4, even more preferably 1-3, most preferably 1-2, consecutive weeks; if subject is a rabbit: 1-5, preferably 1-4, more preferably 1-3, most preferably 2-3, consecutive weeks; if subject is poultry or bird: 1-5, preferably 1-4, more preferably 1-3, even more preferably 2-3, consecutive weeks; if subject is a fish: 1-6, preferably 1-5, more preferably 1-4, even more preferably 2-4, most preferably 3-4, consecutive weeks; if subject is a reptile: 1-12, preferably 1-8, more preferably 1-5, even more preferably 1-3, most preferably 1-2 consecutive weeks;

If subject is human: 1-12, preferably 1-10, more preferably 1-8, even more preferably 1-6, even more preferably 1-5, even more preferably 1-4, even more preferably 1-3, most preferably 1-2, consecutive weeks.

Preferably, said saccharide according to the invention is administered at least once a week (i.e. at least one daily dosage is administered in a week), more preferably at least once every 3 days, even more preferably at least once every 2 days, most preferably at least once daily (i.e. a daily dosage is administered every day).

The inventors have surprisingly found that a saccharide according to the invention is sufficient to obtain an effective therapeutic for preventing and/or treating parasitic disease such as cryptosporidiosis. The presence of other (oligo)saccharides is not required to obtain said therapeutic effect. While the saccharide according to the invention can be administered in a composition including additional components such as saccharides, the present invention relates to the fact that only the saccharide according to the invention is required for achieving an efficient therapeutic effect as described herein.

In an even more preferred embodiment, said saccharide according to the invention is administered to said subject as part of a composition, wherein said saccharide is present at a higher amount or concentration than any mammalian milk oligosaccharide present in said composition. The skilled person will understand that such mammalian milk oligosaccharide(s) can be absent in said composition and that hence the amount or concentration of the saccharide according to the invention is inevitably higher. Further, if one or more mammalian milk oligosaccharides are present in said composition, than the amount or concentration of the saccharide according to the invention (which can be a mammalian milk oligosaccharide or not as defined earlier herein) is higher than said one or more mammalian milk oligosaccharides. In case said saccharide according to the invention is a mammalian milk oligosaccharide, then it is preferred that said saccharide according to the invention is administered to said subject as part of a composition, wherein said saccharide is present at a higher amount or concentration than any other mammalian milk oligosaccharide present in said composition.

Preferably said composition is a pharmaceutical composition and/or a nutritional composition, more preferably a pharmaceutical composition and/or a nutritional composition as described later herein.

In an additional and/or alternative even more preferred embodiment, said saccharide according to the invention is administered to said subject in the absence of lacto-N-neotetraose and/or lacto-N-tetraose and/or sialyllactose, preferably in the absence of lacto-N-neotetraose, more preferably in the absence of lacto-N-neotretraose and lacto-N-tetraose, even more preferably in the absence of lacto-N-neotretraose, lacto-N-tetraose and sialyllactose. In the context of the present invention, the expression "X in the absence of Y" preferably means that the amount of Y constitutes < 10%, preferably < 5.0%, more preferably < 2.0%, even more preferably < 1.0%, most preferably < 0.5%, of the amount of X in a composition administered to said subject. More preferably, said expression means that Y is not present in a composition comprising X.

Composition

In a second aspect, the invention provides a composition for use in a method for preventing and/or treating a parasite infection in a subject, said composition comprises a saccharide comprising a fucose. In an additional and/or alternative embodiment, the invention provides a composition for use in a method for preventing and/or treating cryptosporidiosis in a subject, said composition comprises a saccharide comprising a fucose.

In a preferred embodiment, said composition according to the invention comprises a saccharide as described in the section "saccharide" of the first aspect of the invention.

In an additional and/or alternative preferred embodiment, said parasite infection is as described in the section "parasite infection" of the first aspect of the invention.

In an additional and/or alternative preferred embodiment, said subject is as described in the section "subject" of the first aspect of the invention.

In an additional and/or alternative preferred embodiment, said method for preventing and/or treating is as described in the section "method for preventing and/or treating" of the first aspect of the invention. For example, a preferred embodiment of the second aspect of the invention relates to a composition for use in a method for preventing and/or treating a parasite infection in a subject, said composition comprises a saccharide comprising a fucose, wherein said method comprises administering an effective amount of said saccharide to said subject.

In an additional and/or preferred embodiment, said saccharide of a composition according to the invention is present in said composition at 0.001-5.000 wt. %, preferably 0.001-2.500 wt. %, more preferably 0.001-1.000 wt. %, even more preferably 0.001-0.750 wt. %, even more preferably 0.001-0.500 wt. %, even more preferably 0.002-0.500 wt. %, even more preferably 0.002-0.400 wt. %, most preferably 0.002-0.250 wt. %. In an alternative preferred embodiment, said saccharide of a composition according to the invention is present in said composition at 0.010-1.000 wt. %, preferably 0.010-0.750 wt. %, more preferably 0.010-0.500 wt. %, even more preferably 0.010-0.400 wt. %, even more preferably 0.050-0.400 wt. %, even more preferably 0.100-0.400 wt. %, most preferably 0.100-0.300 wt. % This is for example particularly preferred if said subject is a pig, preferably a piglet. In an alternative preferred embodiment, said saccharide of a composition according to the invention is present in said composition at 0.001-0.250 wt. %, preferably 0.001-0.200 wt. %, more preferably 0.001-0.100 wt. %, even more preferably 0.001- 0.020 wt. %, even more preferably 0.001-0.010 wt. %, even more preferably 0.002-0.010 wt. %, even more preferably 0.003-0.010 wt. %, most preferably 0.003-0.0075 wt. %. This is for example particularly preferred if said subject is bovine, preferably a non-adult bovine.

In a more preferred embodiment, said saccharide of a composition according to the invention is present at a higher amount or concentration than any mammalian milk oligosaccharide present in said composition. The skilled person will understand that such mammalian milk oligosaccharide(s) can be absent in said composition and that hence the amount or concentration of the saccharide according to the invention is inevitably higher. Further, if one or more mammalian milk oligosaccharides are present in said composition, than the amount or concentration of the saccharide according to the invention (which can be a mammalian milk oligosaccharide or not as defined earlier herein) is higher than said one or more mammalian milk oligosaccharides. In case said saccharide according to the invention is a mammalian milk oligosaccharide, then it is preferred that said saccharide according to the invention is present at a higher amount or concentration than any other mammalian milk oligosaccharide present in said composition.

In an additional and/or alternative more preferred embodiment, said composition: does not comprise lacto-N-neotetraose and/or lacto-N-tetraose and/or sialyllactose, preferably does not comprise lacto-N-neotetraose, more preferably does not comprise lacto-N-neotretraose and lacto-N-tetraose, even more preferably does not comprise lacto-N-neotretraose, lacto-N- tetraose and sialyllactose; or comprises any one or more of lacto-N-neotetraose, lacto-N-tetraose and sialyllactose, but at an amount or concentration in the composition which is at least 5, preferably 10, more preferably 15, even more preferably 20, even more preferably 25, even more preferably 50, times lower than the amount or concentration of said saccharide in the composition.

In an additional and/or alternative more preferred embodiment, said saccharide is provided as a powder in a composition according to the invention. Preferably, said powder is as defined in the section "saccharide" of the first aspect.

In an even more preferred embodiment, said composition is a pharmaceutical composition, optionally further comprising a pharmaceutically acceptable carrier, filler, preservative, solubilizer, diluent, excipient, salt, adjuvant and/or solvent.

In an additional and/or alternative even more preferred embodiment, said composition is a nutritional composition, optionally further comprising a feed ingredient and/or a food ingredient, wherein said feed/food ingredient is preferably chosen from the list consisting of: a lipid, preferably one or more selected from the list consisting of an oil, fat, ester, monoglyceride, diglyceride, triglyceride and free fatty acid; a vitamin, preferably one or more selected from the list consisting of vitamin A, vitamin B, vitamin C, vitamin D, vitamin E and vitamin H, or a derivate thereof; an amino acid compound; a trace element; a mineral, preferably one or more selected from the list consisting of calcium, phosphorus, magnesium, iron, zinc, manganese, copper, sodium, potassium, molybdenum, chromium, selenium and chloride; an antioxidant; a prebiotic agent, preferably one or more selected from the list consisting of GOS (galactooligosaccharide), FOS (fructo-oligosaccharide), inulin and resistant starch; a carbohydrate; an antimicrobial agent; and/or a protein.

Generally, any source of protein may be used so long as it is suitable for nutritional compositions and is otherwise compatible with any other selected ingredients or features in the nutritional composition. Nonlimiting examples of suitable proteins (and sources thereof) suitable for use in the nutritional composition according to the invention include, but are not limited to, intact, hydrolyzed, or partially hydrolyzed protein, which may be derived from any known or otherwise suitable source such as milk (e.g., casein, whey), animal (e.g., meat, fish), cereal (e.g., rice, corn, wheat), vegetable (e.g., soy, pea, potato, bean), and combinations thereof. The protein may also include a mixture of amino acids (often described as free amino acids) known for use in nutritional products or a combination of such amino acids with the intact, hydrolyzed, or partially hydrolyzed proteins described herein. The amino acids may be naturally occurring or synthetic amino acids. More particular examples of suitable protein (or sources thereof) used in a nutritional composition according to the invention include, but are not limited to, whole cow's milk, partially or completely defatted milk, milk protein concentrates, milk protein isolates, nonfat dry milk, condensed skim milk, whey protein concentrates, whey protein isolates, acid caseins, sodium caseinates, calcium caseinates, potassium caseinates, legume protein, soy protein concentrates, soy protein isolates, pea protein concentrates, pea protein isolates, collagen proteins, potato proteins, rice proteins, wheat proteins, canola proteins, quinoa, insect proteins, earthworm proteins, fungal (e.g., mushroom) proteins, hydrolyzed yeast, gelatin, bovine colostrum, human colostrum, glycol macropeptides, mycoproteins, proteins expressed by microorganisms (e.g., bacteria and algae), and combinations thereof. A nutritional composition according to the invention may include any individual source of protein or combination of the various sources of protein listed above. In addition, the proteins for use herein can also include, or be entirely or partially replaced by, free amino acids known for use in nutritional products, non-limiting examples of which include L-tryptophan, L-glutamine, L-tyrosine, L-methionine, L-cysteine, taurine, L- arginine, L-carnitine, and combinations thereof.

The carbohydrate or source of carbohydrate suitable for use in a nutritional composition according to the invention may be simple, complex, or variations or combinations thereof. Generally, the carbohydrate may include any carbohydrate or carbohydrate source that is suitable for use nutritional compositions and is otherwise compatible with any other selected ingredients or features in the nutritional composition. Non-limiting examples of carbohydrates suitable for use in the nutritional composition according to the invention, but are not limited to, polydextrose, maltodextrin; hydrolyzed or modified starch or cornstarch; glucose polymers; corn syrup; corn syrup solids; sucrose; glucose; fructose; lactose; high fructose corn syrup; honey; sugar alcohols (e.g., maltitol, erythritol, sorbitol); isomaltulose; sucromalt; pullulan; potato starch; and other slowly-digested carbohydrates; dietary fibers including, but not limited to, fructooligosaccharides (FOS), galactooligosaccharides (GOS), oat fiber, soy fiber, gum arabic, sodium carboxymethylcellulose, methylcellulose, guar gum, gellan gum, locust bean gum, konjac flour, hydroxypropyl methylcellulose, tragacanth gum, karaya gum, gum acacia, chitosan, arabinogalactans, glucomannan, xanthan gum, alginate, pectin, low methoxy pectin, high methoxy pectin, cereal beta-glucans (e.g., oat beta-glucan, barley beta-glucan), carrageenan and psyllium, soluble and insoluble fibers derived from fruits or vegetables; other resistant starches; and combinations thereof. A nutritional composition according to the invention may include any individual source of carbohydrate or combination of the various sources of carbohydrate listed above.

The fat or source of fat suitable for use in a nutritional composition according to the invention may be derived from various sources including, but not limited to, plants, animals, and combinations thereof. Generally, the fat may include any fat or fat source that is suitable for use in a nutritional composition according to the invention and is otherwise compatible with any other selected ingredients or features in the nutritional composition. Non-limiting examples of suitable fat (or sources thereof) for use in a nutritional composition according to the invention include coconut oil, fractionated coconut oil, soy oil, high oleic soy oil, corn oil, olive oil, safflower oil, high oleic safflower oil, medium chain triglyceride oil (MCT oil), high gamma linolenic (GLA) safflower oil, sunflower oil, high oleic sunflower oil, palm oil, palm kernel oil, palm olein, canola oil, high oleic canola oil, marine oils, fish oils, algal oils, borage oil, cottonseed oil, fungal oils, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (ARA), conjugated linoleic acid (CLA), alpha-linolenic acid, rice bran oil, wheat bran oil, interesterified oils, transesterified oils, structured lipids, and combinations thereof. Generally, the fats used in a nutritional composition for formulating infant formulas and paediatric formulas provide fatty acids needed both as an energy source and for the healthy development of the infant, toddler, or child. These fats typically comprise triglycerides, although the fats may also comprise diglycerides, monoglycerides, and free fatty acids. Fatty acids provided by the fats in the nutritional composition include, but are not limited to, capric acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, oleic acid, linoleic acid, alphalinolenic acid, ARA, EPA, and DHA. The nutritional composition can include any individual source of fat or combination of the various sources of fat listed above. Preferably, the fat is a mixture of vegetable fat and milk fat such as obtained from milk from a mammal like cow, sheep, goat, mare, or camel. More preferably, wherein the milk fat is bovine milk fat. Mixtures of different types of fat are preferred because they help to provide different fatty acids and better resemble the type of linkage between the glycerol moiety and the fatty acid moiety in the fat, when compared to human mother's milk.

When one or more prebiotics is/are present, then it is preferred that the weight ratio between the saccharide according to the invention and said prebiotic(s) is in the range of from 0.5:10 to 10:0.5.

In a preferred embodiment, said pharmaceutical or nutritional composition according to the invention comprises one or more probiotics for its beneficial effect on the subject's gut microbiome. Examples of probiotics include Bifidobacterium, Lactobacillus and Saccharomyces boulardii.

In a more preferred embodiment, said nutritional composition is a synthetic nutritional composition. In the context of the present invention, a "synthetic composition" or a "synthetic nutritional composition" refers to a composition which is artificially prepared and preferably refers to a composition comprising at least one component that is produced ex vivo, either chemically and/or biologically, e.g. by means of chemical reaction, enzymatic reaction or recombinantly, or purified by humans. It is preferred that a synthetic nutritional composition of the invention is not identical with a naturally occurring composition.

In an additional and/or alternative more preferred embodiment, said nutritional composition is a food product, preferably wherein said food product is selected from a list consisting of dairy product, bar, liquid product, savory snack, savory biscuit, bakery product, pasta and food supplement, more preferably wherein said food product is selected from a list consisting of dairy product, liquid product and food supplement.

In an additional and/or alternative more preferred embodiment, said nutritional composition is selected from a list consisting of infant formula, baby food, infant cereal composition, growing-up milk, milk replacer, creep feed, pet food, dry feed, frozen feed, pre weaning feed, weaning feed and post weaning feed.

In an alternative more preferred embodiment, said nutritional composition is selected from a list consisting of milk replacer, creep feed, pet food, prestarter diet, pre weaning feed, weaning feed and post weaning feed, preferably selected from a list consisting of pre weaning feed, weaning feed and post weaning feed.

In an even more preferred embodiment, said nutritional composition is a milk replacer or a creep feed, preferably wherein said nutritional composition is a milk replacer or preferably wherein said nutritional composition is a creep feed.

In the context of the present invention, an "infant formula" refers to to a nutritional composition that has the proper balance of macronutrients, micro-nutrients, and calories to provide sole or supplemental nourishment for and generally maintain or improve the health of infants, toddlers, or both. Infant formulas preferably comprise nutrients in accordance with the relevant infant formula guidelines for the targeted consumer or user population, an example of which would be the Infant Formula Act, 21 U.S.C. Section 350(a). Another example with guidelines for nutrients of an infant formula, in particular for a person of 0-12 months of age and for children up to 36 months old, may be found in the CODEX Alimentarius (CODEX STAN 72-1981), further referred to as the CODEX). Nutritional compositions for infants are commonly referred to as infant formula. When used as infant formula, the nutritional composition according to the invention should contain the ingredients in the amounts as prescribed by the CODEX and, if needed, as prescribed by additional regulations of individual countries. The protein component is typically present in an amount of from 5% to 35% by weight of the infant formula (i.e., the dry weight), including from 10% to 30%, from 10% to 25%, from 15% to 25%, from 20% to 30%, from 15% to 20%, and also including from 10% to 16% by weight of the infant formula (i.e., the dry weight). The carbohydrate component is typically present in an amount of from 40% to 75% by weight of the infant formula (i.e., the dry weight), including from 45% to 75%, from 45% to 70%, from 50% to 70%, from 50% to 65%, from 50% to 60%, from 60% to 75%, from 55% to 65%, and also including from 65% to 70% by weight of the infant formula (i.e., the dry weight). The fat component is typically present in an amount of from 10% to 40% by weight of the infant formula (i.e., the dry weight), including from 15% to 40%, from 20% to 35%, from 20% to 30%, from 25% to 35%, and also including from 25% to 30% by weight of the infant formula (i.e., the dry weight).

In the context of the present invention, "growing-up milk" refers to a milk-based beverage adapted for the specific nutritional needs of young children.

In the context of the invention, the term "weaning" or "weaning period" refers to the period during which the mother's milk is substituted by other food in the diet.

In the context of the invention, the term "creep feed" refers to a nutritional composition which is used to supplement a pre-weaned subject with a solid diet while said subject is suckling. For example, a piglet receives creep feed to ease the transition from sow's milk to solid pig starter feed. The creep feed stimulates the digestive system of the piglet to produce e.g. amylase which digests carbohydrates in dry feed. If a pig is better able to digest dry feed, he can start eating quickly post-weaning for better performance.

In the context of the invention, the term "milk replacer" refers to a nutritional composition which serves as a substitute for mother's milk. A milk replacer comprises milk proteins, fat, carbohydrates, vitamins and minerals. Preferably, a milk replacer comprises 20 wt. % to 30 wt. % water, 18 wt. % to 24 wt. % of at least one protein, 15 wt. % to 28 wt. % (preferably 20 wt. % to 25 wt. %) of at least one fat and lactose at < 50 wt. %.

Method for preventing and/or treating a parasite infection

In a third aspect, the invention provides a method for preventing and/or treating a parasite infection in a subject as defined in the previous sections. The method comprises administering a saccharide comprising a fucose (as described in the section "saccharide" of the first aspect) or a composition (as described in the second aspect) of the invention to said subject.

In an additional and/or alternative preferred embodiment, the invention provides a method for preventing and/or treating cryptosporidiosis. The latter is a parasitic disease caused by a Cryptosporidium species, preferably as described herein (it is referred to section "parasite infection" of the first aspect). Throughout the application, unless specifically stated otherwise, "method for preventing and/or treating a parasite infection" is preferably replaced with "method for preventing and/or treating cryptosporidiosis".

Use

In a fourth aspect, the invention provides the use of a saccharide comprising a fucose (as described in the section "saccharide" of the first aspect) or a composition (as described in the second aspect) according to the invention for the manufacture of a medicament for preventing and/or treating a parasite infection in a subject as defined in the previous sections.

In an additional and/or alternative preferred embodiment, the invention provides said use for the manufacture of a medicament for preventing and/or treating cryptosporidiosis. The latter is a parasitic disease caused by a Cryptosporidium species, preferably as described herein (it is referred to section "parasite infection" of the first aspect). Throughout the application, unless specifically stated otherwise, "manufacture of a medicament for preventing and/or treating a parasite infection" is preferably replaced with "manufacture of a medicament for preventing and/or treating cryptosporidiosis".

Specific embodiments

The present invention preferably relates to the following specific embodiments: . A saccharide comprising a fucose for use in a method for preventing and/or treating a parasite infection in a subject, preferably wherein said parasite is a single-celled parasite, more preferably said parasite is a single-celled protozoan. . A saccharide for use according to embodiment 1, wherein said parasite is a Cryptosporidium species, preferably wherein said parasite is selected from a list consisting of Cryptosporidium parvum, Cryptosporidium suis, Cryptosporidium scrofarum, Cryptosporidium hominis, Cryptosporidium bovis, Cryptosporidium andersoni, Cryptosporidium ruyanae, Cryptosporidium felis, Cryptosporidium canis, Cryptosporidium meleagridis, Cryptosporidium baileyi, Cryptosporidium cuniculus, Cryptosporidium xiaoi, Cryptosporidium ubiquitum, Cryptosporidium viatorum, Cryptosporidium muris, Cryptosporidium molnari, Cryptosporidium scophthalmi, Cryptosporidium huw, Cryptosporidium serpentis and Cryptosporidium varanii, more preferably wherein said parasite is selected from a list consisting of Cryptosporidium parvum, Cryptosporidium suis, Cryptosporidium scrofarum, Cryptosporidium hominis, Cryptosporidium bovis, Cryptosporidium andersoni, Cryptosporidium galli and Cryptosporidium ruyanae, even more preferably wherein said parasite is selected from a list consisting of Cryptosporidium parvum, Cryptosporidium suis and Cryptosporidium scrofarum, most preferably wherein said parasite is Cryptosporidium parvum.

3. A saccharide for use according to embodiment 1 or 2, wherein said saccharide is for use in a method for preventing and/or treating cryptosporidiosis.

4. A saccharide for use according to any one of embodiments 1 to 3, wherein said saccharide is a disaccharide or an oligosaccharide, preferably said saccharide is an oligosaccharide.

5. A saccharide for use according to embodiment 4, wherein said saccharide consists of 3-9, preferably 3-8, more preferably 3-7, even more preferably 3-6, even more preferably 3-5, monosaccharides.

6. A saccharide for use according to any one of embodiments 1 to 5, wherein said saccharide is a neutral saccharide.

7. A saccharide for use according to any one of embodiments 4 to 6, wherein said saccharide is a mammalian milk oligosaccharide (MMO), preferably a human milk oligosaccharide (HMO).

8. A saccharide for use according to any one of embodiments 1 to 7, wherein said fucose is linked to a monosaccharide in an alpha-1,2-, alpha-1,3- or alpha-1, 4-linkage, preferably an alpha-1,2- or an alpha- 1,3-linkage, more preferably an alpha-1, 2-linkage, and wherein said monosaccharide is preferably selected from glucose, N-acetylglucosamine and galactose, more preferably said monosaccharide is glucose or galactose, even more preferably said monosaccharide is galactose.

9. A saccharide for use according to any one of embodiments 4 to 8, wherein said saccharide comprises a lactose, a lacto-N-biose (LNB) or N-acetyllactosamine (LacNAc) at its reducing end, preferably said saccharide comprises a lactose at is reducing end.

10. A saccharide for use according to any one of embodiments 4 to 9, wherein said saccharide is selected from a list consisting of 2'-fucosyllactose (2'FL), 3-fucosyllactose (3-FL), difucosyllactose (diFL), 2'- fucosyl-N-acetyllactosamine (2'FlacNAc), difucosyl-N-acetyllactosamine (diFLacNAc), 3-fucosyl-N- acetyllactosamine (3FlacNAc), 2'-fucosyllacto-N-biose (2'FLNB), 4-fucosyllacto-N-biose (4FLNB), difucosyllacto-N-biose (diFLNB), lacto-N-fucopentaose I (LNFP I), blood group A antigen hexaose type 1 (GalNAc-LNFP I), blood group B antigen hexaose type 1 (Gal-LNFP I), lacto-N-fucopentaose II (LNFP

II), lacto-N-fucopentaose III (LNFP III), lacto-N-fucopentaose V (LNFP V), lacto-N-difucohexaose I (LNDFH I), lacto-N-difucohexaose II (LNDFH II), lewis b-lewis x, monofucosyllacto-N-hexaose III (MFLNH

III), difucosyllacto-N-hexaose (a) (DFLNH (a)), difucosyllacto-N-hexaose (DFLNH), trifucosyllacto-N- hexaose (TFLNH), lacto-N-neofucopentaose I (LNnFP I), lacto-N-neofucopentaose V (LNnFP V, LNFP VI), and lacto-N-neodifucohexaose (LNnDFH).

11. A saccharide for use according to any one of embodiments 4 to 9, wherein said saccharide is selected from a list consisting of 2'FL, diFL, LNFP I, GalNAc-LNFP I, Gal-LNFP I, LNDFH I, lewis b-lewis x, DFLNH (a), TFLNH, 2'FLNB, diFLNB, 2'FlacNAc and diFLacNAc, preferably selected from a list consisting of 2'FL, di FL, LNFP I, 2'FLNB, diFLNB, 2'FlacNAc and diFLacNAc, more preferably selected from a list consisting of 2'FL, diFL, 2'FLNB, diFLNB, 2'FlacNAc and diFLacNAc, even more preferably selected from a list consisting of 2'FL, 2'FLNB and 2'FlacNAc, even more preferably wherein said saccharide is 2'FL or diFL, most preferably wherein said saccharide is 2'FL.

12. A saccharide for use according to any one of embodiments 1 to 11, wherein said saccharide has been produced, preferably in vitro and/or ex vivo, by a cell, preferably a single cell, wherein said cell is preferably chosen from the list consisting of a microorganism, a plant cell, an animal cell or a protozoan cell.

13. A saccharide for use according to any one of embodiments 1 to 12, wherein said saccharide is linked, preferably chemically linked, to a carrier for delivery of said saccharide.

14. A saccharide for use according to embodiment 13, wherein said carrier is a ceramide-based carrier or a polypeptide-based carrier, preferably a ceramide-based carrier, wherein said ceramide-based carrier is preferably selected from a list consisting of dl8:l/16:0, tl8:0-16:0, tl8:0-hl6:0, tl8:0-h22:0 and tl8:0-h24:0.

15. A saccharide for use according to any one of embodiments 1 to 13, wherein said subject is a human or an animal, preferably said subject is an animal.

16. A saccharide for use according to embodiment 15, wherein said animal is selected from a list consisting of a farmed animal, a horse, a companion animal, a bird, a fish and a reptile, preferably wherein said animal is a farmed animal, more preferably wherein said animal is a farmed animal selected from a list consisting of pig, bovine, horse, sheep, goat, camelid, rabbit and poultry, even more preferably wherein said animal is a pig, bovine or horse, even more preferably wherein said animal is a pig or bovine, most preferably wherein said animal is a pig.

17. A saccharide for use according to any one of embodiments 1 to 16, wherein said subject is an adult or a non-adult subject, preferably a non-adult subject.

18. A saccharide for use according to embodiment 17, wherein said subject is a non-adult human, preferably an infant (age of 0-1 year) or a child of 1-9 years, more preferably an infant (age of 0-1 year) or a child of 1-6 years, even more preferably an infant (age of 0-1 year) or a child of 1-4 years.

19. A saccharide for use according to embodiment 17, wherein said subject is a non-adult animal, preferably selected from a list consisting of piglet, calf, foal, lamb, kid, cria, kitten, chick and puppy, more preferably selected from a list consisting of piglet, calf, foal, lamb, kid, cria, kitten and chick, even more preferably a piglet, calf or foal, even more preferably a piglet or calf, most preferably a piglet.

20. A saccharide for use according to any one of embodiments 1 to 19, wherein said method comprises administering an effective amount of said saccharide to said subject.

21. A saccharide for use according to any one of embodiments 1 to 20, wherein said saccharide is administered at a daily dose of 0.01-150.0 mg, preferably 0.01-125.0 mg, more preferably 0.01-100.0 mg, even more preferably 0.01-80.0 mg, per kg bodyweight of said subject.

22. A saccharide for use according to any one of embodiments 1 to 20, wherein said saccharide is administered at a daily dose of 1.0-150.0 mg, preferably 1.0-125.0 mg, more preferably 5.0-125.0 mg, even more preferably 10.0-125.0 mg, even more preferably 10.0-100.0 mg, even more preferably 10.0-80.0 mg, even more preferably 15.0-80.0 mg, even more preferably 20.0-80.0 mg, even more preferably 25.0-80.0 mg, even more preferably 30.0-80.0 mg, even more preferably 35.0-80.0 mg, even more preferably 40.0-80.0 mg, most preferably 45.0-80.0 mg, per kg bodyweight of said subject.

23. A saccharide for use according to any one of embodiments 1 to 20, wherein said saccharide is administered at daily dose of 0.01-50.0 mg, preferably 0.01-30.0 mg, more preferably 0.01-25.0 mg, even more preferably 0.01-20.0 mg, even more preferably 0.01-15.0 mg, even more preferably 0.01- 10.0 mg, even more preferably 0.05-10.0 mg, most preferably 0.1-10.0 mg, per kg bodyweight of said subject.

24. A saccharide for use according to any one of embodiments 1 to 23, wherein said saccharide is administered at a daily dose of 0.01-15.0 g, preferably 0.01-10.0 g, more preferably 0.01-5.0 g, even more preferably 0.01-2.0 g, even more preferably 0.01-1.0 g, even more preferably 0.015-1.0 g, most preferably 0.02-1.0 g.

25. A saccharide for use according to any one of embodiments 1 to 23, wherein said saccharide is administered at a daily dose of 0.01-5.0 g, preferably 0.1-2.5 g, more preferably 0.1-1.5 g, even more preferably 0.1-1.2 g, even more preferably 0.2-1.2 g, even more preferably 0.3-1.2 g, even more preferably 0.4-1.2 g, most preferably 0.5-1.2 g.

26. A saccharide for use according to any one of embodiments 1 to 23, wherein said saccharide is administered at a daily dose of 0.01-1.0 g, preferably 0.01-0.75 g, more preferably 0.01-0.65 g, even more preferably 0.01-0.60 g, even more preferably 0.01-0.50 g, even more preferably 0.015-0.50 g, even more preferably 0.015-0.40 g, even more preferably 0.015-0.30 g, most preferably 0.015-0.20 g.

27. A saccharide for use according to any one of embodiments 1 to 26, wherein said saccharide is administered to said subject at least once between birth (0 weeks) and 5 weeks of age, preferably between birth and 4 weeks of age, more preferably between birth and 3 weeks of age.

28. A saccharide for use according to any one of embodiments 1 to 27, wherein said saccharide is administered to said subject for 1-30, preferably 1-25, more preferably 1-20, even more preferably 1- 15, even more preferably 1-10, even more preferably 1-7.5, even more preferably 1-5, even more preferably 1-4, most preferably 1-3, consecutive weeks.

29. A saccharide for use according to any one of embodiments 1 to 28, wherein said saccharide is administered to said subject for: if subject is a pig: 1-5, preferably 1-4, more preferably 1-3, most preferably 2-3, consecutive weeks; if subject is bovine: 1-36, preferably 1-32, more preferably 1-30, even more preferably 1-28, even more preferably 1-26, even more preferably 1-18, even more preferably 1-12, even more preferably 1-6, most preferably 1-4, consecutive weeks; if subject is a dog: 1-5, preferably 1-4, more preferably 1-3, most preferably 2-3, consecutive weeks; if subject is a cat: 1-5, preferably 1-4, more preferably 1-3, most preferably 2-3, consecutive weeks; if subject is a horse: 1-12, preferably 1-8, more preferably 1-5, even more preferably 1-3, most preferably 1-2, consecutive weeks; if subject is a sheep: 1-36, preferably 1-32, more preferably 1-30, even more preferably 1-28, even more preferably 1-26, even more preferably 1-18, even more preferably 1-12, even more preferably 1-6, most preferably 1-4, consecutive weeks; if subject is a goat: 1-36, preferably 1-32, more preferably 1-30, even more preferably 1-28, even more preferably 1-26, even more preferably 1-18, even more preferably 1-12, even more preferably 1-6, most preferably 1-4, consecutive weeks; if subject is a camelid: 1-12, preferably 1-10, more preferably 1-8, even more preferably 1-6, even more preferably 1-5, even more preferably 1-4, even more preferably 1-3, most preferably 1-2, consecutive weeks; if subject is a rabbit: 1-5, preferably 1-4, more preferably 1-3, most preferably 2-3, consecutive weeks; if subject is poultry or bird: 1-5, preferably 1-4, more preferably 1-3, most preferably 2-3, consecutive weeks; if subject is a fish: 1-6, preferably 1-5, more preferably 1-4, even more preferably 2-4, most preferably 3-4, consecutive weeks; if subject is a reptile: 1-12, preferably 1-8, more preferably 1-5, even more preferably 1-3, most preferably 1-2, consecutive weeks; if subject is a human: 1-12, preferably 1-10, more preferably 1-8, even more preferably 1-6, even more preferably 1-5, even more preferably 1-4, even more preferably 1-3, most preferably 1-2, consecutive weeks. A saccharide for use according to any one of embodiments 1 to 29, wherein said saccharide is administered to said subject as part of a composition, wherein said saccharide is present at a higher amount than any mammalian milk oligosaccharide present in said composition, preferably wherein said composition is a pharmaceutical composition and/or a nutritional composition. A saccharide for use according to any one of embodiments 1 to 30, wherein said saccharide is administered to said subject in the absence of lacto-N-neotetraose and/or lacto-N-tetraose and/or sialyllactose, preferably in the absence of lacto-N-neotetraose, more preferably in the absence of lacto-N-neotretraose and lacto-N-tetraose, even more preferably in the absence of lacto-N- neotretraose, lacto-N-tetraose and sialyllactose. A composition for use in a method for preventing and/or treating a parasite infection in a subject, said composition comprises a saccharide comprising a fucose, preferably said saccharide is as defined in any one of embodiments 4 to 14, wherein said parasite is preferably a single-celled parasite, more preferably said parasite is a single-celled protozoan, even more preferably said parasite is as defined in embodiment 2.

33. A composition for use according to embodiment 32, wherein said composition is for use in a method for preventing and/or treating cryptosporidiosis.

34. A composition for use according to embodiment 32 or 33, wherein said subject is as defined in any one of embodiments 15 to 19.

35. A composition for use according to any one of embodiments 32 to 34, wherein said saccharide is present in said composition at 0.001-5.000 wt. %, preferably 0.001-2.500 wt. %, more preferably 0.001- 1.000 wt. %, even more preferably 0.001-0.750 wt. %, even more preferably 0.001-0.500 wt. %, even more preferably 0.002-0.500 wt. %, even more preferably 0.002-0.400 wt. %, most preferably 0.002- 0.250 wt. %.

36. A composition for use according to any one of embodiments 32 to 34, wherein said saccharide is present in said composition at 0.010-1.000 wt. %, preferably 0.010-0.750 wt. %, more preferably 0.010- 0.500 wt. %, even more preferably 0.010-0.400 wt. %, even more preferably 0.050-0.400 wt. %, even more preferably 0.100-0.400 wt. %, most preferably 0.100-0.300 wt. %.

37. A composition for use according to any one of embodiments 32 to 34, wherein said saccharide is present in said composition at 0.001-0.250 wt. %, preferably 0.001-0.200 wt. %, more preferably 0.001- 0.100 wt. %, even more preferably 0.001-0.020 wt. %, even more preferably 0.001-0.010 wt. %, even more preferably 0.002-0.010 wt. %, even more preferably 0.003-0.010 wt. %, most preferably 0.003- 0.0075 wt. %.

38. A composition for use according to any one of embodiments 32 to 37, wherein said method comprises administering an effective amount of said saccharide to said subject, preferably wherein said saccharide is administered at a daily dose as defined in any one of embodiments 21 to 26.

39. A composition for use according to any one of embodiments 32 to 38, wherein said composition is administered to said subject as defined in any one of embodiments 27 to 31.

40. A composition for use according to any one of embodiments 32 to 39, wherein said saccharide is present at a higher amount than any mammalian milk oligosaccharide present in said composition.

41. A composition for use according to any one of embodiments 32 to 40, wherein said composition: does not comprise lacto-N-neotetraose and/or lacto-N-tetraose and/or sialyllactose, preferably does not comprise lacto-N-neotetraose, more preferably does not comprise lacto-N-neotretraose and lacto-N-tetraose, even more preferably does not comprise lacto-N-neotretraose, lacto-N- tetraose and sialyllactose; or comprises any one or more of lacto-N-neotetraose, lacto-N-tetraose and sialyllactose, but at an amount in the composition which is at least 5, preferably 10, more preferably 15, even more preferably 20, even more preferably 25, even more preferably 50, times lower than the concentration of said saccharide in the composition. A composition for use according to any one of embodiments 32 to 41, wherein said composition is a pharmaceutical composition, optionally further comprising a pharmaceutically acceptable carrier, filler, preservative, solubilizer, diluent, excipient, salt, adjuvant and/or solvent. A composition for use according to any one of embodiments 32 to 41, wherein said composition is a nutritional composition, optionally further comprising a feed ingredient and/or a food ingredient, wherein said feed/food ingredient is preferably chosen from the list consisting of: a lipid, preferably one or more selected from the list consisting of an oil, fat, ester, monoglyceride, diglyceride, triglyceride and free fatty acid; a vitamin, preferably one or more selected from the list consisting of vitamin A, vitamin B, vitamin C, vitamin D, vitamin E and vitamin H, or a derivate thereof; an amino acid compound; a trace element; a mineral; an antioxidant; a prebiotic agent; a carbohydrate; an antimicrobial agent; and/or a protein. A composition for use according to embodiment 43, wherein said nutritional composition is a synthetic nutritional composition. A composition for use according to embodiment 43 or 44, wherein said nutritional composition is a food product, preferably wherein said food product is selected from a list consisting of dairy product, bar, liquid product, savory snack, savory biscuit, bakery product, pasta and food supplement, more preferably wherein said food product is selected from a list consisting of dairy product, liquid product and food supplement. A composition for use according to embodiment 43 or 44, wherein said nutritional composition is selected from a list consisting of infant formula, baby food, infant cereal composition, growing-up milk, milk replacer, creep feed, pet food, dry feed, frozen feed, pre weaning feed, weaning feed and post weaning feed. A composition for use according to embodiment 43 or 44, wherein said nutritional composition is selected from a list consisting of milk replacer, creep feed, pet food, prestarter diet, pre weaning feed, weaning feed and post weaning feed, preferably selected from a list consisting of pre weaning feed, weaning feed and post weaning feed, more preferably wherein said nutritional composition is a milk replacer or a creep feed, most preferably wherein said nutritional composition is a milk replacer. 48. A method for preventing and/or treating a parasite infection in a subject, wherein said method comprises administering a saccharide comprising a fucose, preferably a saccharide as defined in any one of embodiments 4 to 14, or a composition according to any one of embodiments 32 to 47.

49. A method according to embodiment 48, wherein said parasite is a single-celled parasite, preferably said parasite is a single-celled protozoan, more preferably said parasite is as defined in embodiment 2.

50. A method according to embodiment 48 or 49, wherein said method is for preventing and/or treating cryptosporidiosis.

51. A method according to any one of embodiments 48 to 50, wherein said subject is as defined in any one of embodiments 15 to 19.

52. A method according to any one of embodiments 48 to 51, wherein said method comprises administering an effective amount of said saccharide to said subject, preferably wherein said saccharide is administered as defined in any one of embodiments 21 to 31.

53. Use of a saccharide comprising a fucose, preferably a saccharide as defined in any one of embodiments 4 to 14, or a composition according to any one of embodiments 32 to 47, for the manufacture of a medicament for preventing and/or treating a parasite infection in a subject.

54. Use according to embodiment 53, wherein said parasite is a single-celled parasite, preferably said parasite is a single-celled protozoan, more preferably said parasite is as defined in embodiment 2.

55. Use according to embodiment 53 or 54, wherein said medicament is for preventing and/or treating cryptosporidiosis.

56. Use according to any one of embodiments 53 to 55, wherein said subject is as defined in any one of embodiments 15 to 19.

57. Use according to any one of embodiments 53 to 56, wherein an effective amount of said saccharide is administered to said subject, preferably wherein said saccharide is administered as defined in any one of embodiments 21 to 31.

Definitions

The words used in this specification to describe the invention and its various embodiments are to be understood not only in the sense of their commonly defined meanings, but to include by special definition in this specification structure, material or acts beyond the scope of the commonly defined meanings. Thus, if an element can be understood in the context of this specification as including more than one meaning, then its use in a claim must be understood as being generic to all possible meanings supported by the specification and by the word itself.

The various aspects and embodiments of the invention disclosed herein are to be understood not only in the order and context specifically described in this specification, but to include any order and any combination thereof. Each embodiment as identified herein may be combined together unless otherwise indicated. All patent and literature references cited in the present specification are hereby incorporated by reference in their entirety. Unless specifically stated otherwise, all words used in the singular number shall be deemed to include the plural and vice versa. Unless defined otherwise, all technical and scientific terms used herein generally have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Generally, the nomenclature used herein and the laboratory procedures in cell culture, molecular genetics, organic chemistry and nucleic acid chemistry and hybridization described herein are those well-known and commonly employed in the art. Standard techniques are used for nucleic acid and peptide synthesis. Generally, enzymatic reactions and purification steps are performed according to the manufacturer's specifications.

In the drawings and specification, there have been disclosed embodiments of the invention, and although specific terms are employed, the terms are used in a descriptive sense only and not for purposes of limitation, the scope of the invention being set forth in the following claims. It must be understood that the illustrated embodiments have been set forth only for the purposes of example and that it should not be taken as limiting the invention. It will be apparent to those skilled in the art that alterations, other embodiments, improvements, details and uses can be made consistent with the letter and spirit of the invention herein and within the scope of this invention, which is limited only by the claims, construed in accordance with the patent law, including the doctrine of equivalents. In the claims which follow, reference characters used to designate claim steps are provided for convenience of description only, and are not intended to imply any particular order for performing the steps (unless specifically stated otherwise).

In this document and in its claims, the verbs "to comprise", "to have" and "to contain", and their conjugations are used in their non-limiting sense to mean that items following the word are included, but items not specifically mentioned are not excluded. The verb "to consist essentially of" means that e.g. a composition as defined herein may comprise additional component(s) than the ones specifically identified, said additional component(s) not altering the unique characteristic of the invention. Throughout the document and claims, unless specifically stated otherwise, the verbs "to comprise", "to have" and "to contain", and their conjugations, may be preferably replaced by "to consist" (and its conjugations) or "to consist essentially of" (and its conjugations) and vice versa. In addition, reference to an element by the indefinite article "a" or "an" does not exclude the possibility that more than one of the element is present, unless the context clearly requires that there be one and only one of the elements. The indefinite article "a" or "an" thus usually means "at least one". The word "about" or "approximately" or "around" when used in association with a numerical value (e.g. about 10) preferably means that the value may be the given value (of 10) more or less 10%, preferably 5%, more preferably 1% of the value.

The term "polysaccharide" as used in the context of the present invention refers to a saccharide containing a plurality of repeating units comprised of simple sugars. In the context of the invention, said polysaccharide preferably has a degree of polymerization which is at least 40 (and preferably < 3000).

The terms "LNT II", "LNT-II", "LN3", "lacto-N-triose II", "lacto-N-triose II", "lacto-N-triose", "lacto-N-triose" and "GlcNAcpi-3Gaipi-4Glc" are used interchangeably.

The terms "LNT", "lacto-N-tetraose", "lacto-/V-tetraose" and "Gaipi-3GlcNAcpi-3Gaipi-4Glc" are used interchangeably.

The terms "LNnT", "lacto-N-neotetraose", "lacto-/V-neotetraose", "neo-LNT" and "Gaipi-4GlcNAcpi- 3Gaipi-4Glc" are used interchangeably.

The terms "2' fucosyllactose", "2'-fucosyllactose", "alpha-1, 2-fucosyllactose", "alpha 1,2 fucosyllactose", "a-l,2-fucosyllactose", "a 1,2 fucosyllactose", "Gaip-4(Fucal-2)Glc", 2FL" and "2'FL" are used interchangeably.

The terms "3-fucosyllactose", "alpha-1, 3-fucosyllactose", "alpha 1,3 fucosyllactose", "a-1,3- fucosyllactose", "a 1,3 fucosyllactose", "Gaip-4(Fucal-3)Glc", 3FL" and "3-FL" are used interchangeably. The terms "difucosyllactose", "di-fucosyllactose", "lactodifucotetraose", "2',3-difucosyllactose", "2', 3 difucosyllactose", "a-2', 3-fucosyllactose", "a 2', 3 fucosyllactose, "Fucal-2Gaipi-4(Fucal-3)Glc", "DFLac", 2', 3 diFL", "DFL", "DiFL" and "di FL" are used interchangeably.

The terms "2'-fucosyl-N-acetyllactosamine", "2'FlacNAc" oand "Fucal-2Gaipi-4GlcNAc" are used interchangeably.

The terms "3-fucosyl-N-acetyllactosamine", "3FlacNAc" and "Gaipi-4(Fucal-3)GlcNAc" are used interchangeably.

The terms "difucosyl-N-acetyllactosamine", "diFlacNAc" and "Fucal-2Gaipi-4[Fucal-3]GlcNAc" are used interchangeably.

The terms "2'-fucosyllacto-N-biose", "2'FLNB" and "Fucal-2Gaipi-3GlcNAc" are used interchangeably.

The terms "4-fucosyllacto-N-biose", "4FLNB" and "Fucal-4[Gaipi-3]GlcNAc" are used interchangeably.

The terms "difucosyllacto-N-biose", "diFLNB" and "Fucal-4[Fucal-2Gaipi-3]GlcNAc" are used interchangeably.

The terms "LNFP-I", "lacto-N-fucopentaose I", "LNFP I", "LNF I OH type I determinant", "LNF I", "LNF1", "LNF 1", "Blood group H antigen pentaose type 1" and "Fuc-al,2-Gal-pi,3-GlcNAc-pi,3-Gal-pi,4-Glc" are used interchangeably.

The terms "Gal-LNFP-I", "blood group B antigen hexaose type I" and "Gal-al,3-(Fuc-al,2)-Gal-pi,3- GlcNAc-pi,3-Gal-pi,4-Glc" are used interchangeably.

The terms "GalNAc-LNFP-l", "blood group A antigen hexaose type I", and "GalNAc-al,3-(Fuc-al,2)-Gal- pi,3-GlcNAc- pi,3-Gal-pi,4-Glc" are used interchangeably.

The terms "LNFP-II", "lacto-N-fucopentaose II" and "Gal-pi,3-(Fuc-al,4)-GlcNAc-pi,3-Gal-pi,4-Glc" are used interchangeably.

The terms "LNFP-III", "lacto-N-fucopentaose III" and "Gal-pi,4-(Fuc-al,3)-GlcNAc-pi,3-Gal-pi,4-Glc" are used interchangeably. The terms "LNFP-V", "lacto-N-fucopentaose V" and "Gal-pi,3-GlcNAc-pi,3-Gal-pi,4-(Fuc-al,3)-Glc" are used interchangeably.

The terms "LNDFH I", "Lacto-N-difucohexaose I", "LNDFH-I", "LDFH I", "Le ^b -lactose", "Lewis-b hexasaccharide" and "Fuc-al,2-Gal-pi,3-[Fuc-al,4]-GlcNAc-pi,3-Gal-pi,4-Glc" are used interchangeably. The terms "LNDFH II", "Lacto-N-difucohexaose II", "Lewis a-Lewis x", "LDFH II" and "Fuc-al,4-(Gal-pi,3)- GlcNAc-pi,3-Gal-pi,4-(Fuc-al,3)-Glc" are used interchangeably.

The terms "lewis b-lewis x" and "Fucal,4-[Fuc-al,2-Gaipi,3]-GlcNAc-pi,3-Gal-pi,4-[Fuc-al,3]- Glc are used interchangeably.

The terms "MFLNH III", "monofucosyllacto-N-hexaose-lll" and "Gal-pi,4-[Fuc-al,3]-GlcNAc-pi,6-[Gal- pi,3-GlcNAc-pi,3]-Gal-pi,4-Glc" are used interchangeably.

The terms "DFLNH (a)", "difucosyllacto-N-hexaose (a)" and "Gal-pi,4-[Fuc-al,3]-GlcNAc-pi,6-[Fuc-al,2- Gal-pi,3-GlcNAc-pi,3]-Gal-pi,4-Glc" are used interchangeably.

The terms "DFLNH", "difucosyllacto-N-hexaose" and "Gal-pi,4-[Fuc-al,3]-GlcNAc-pi,6-[Fuc-al,4-[Gal- pi,3]-GlcNAc-pi,3]-Gal-pi,4-Glc" are used interchangeably.

The terms "TFLNH", "trifucosyllacto-N-hexaose" and "Gal-pi,4-[Fuc-al,3]-GlcNAc-pi,6-[Fuc-al,4-[Fuc- al,2-Gal-pi,3]-GlcNAc-pi,3]-Gal-pi,4-Glc" are used interchangeably.

The terms "LNnFP I", "Lacto-N-neofucopentaose I" and "Fuc-al,2-Gal-pi,4-GlcNAc-pi,3-Gal-pi,4-Glc" are used interchangeably.

The terms "LNFP-VI", "LNnFP V", "lacto-N-neofucopentaose V" and "Gal-pi,4-GlcNAc-pi,3-Gal-pi,4-(Fuc- al,3)-Glc" are used interchangeably.

The terms "LNnDFH", "Lacto-N-neoDiFucohexaose", "Lewis x hexaose" "Gal-pi,4-(Fuc-al,3)-GlcNAc-pi,3- Gal-pi,4-(Fuc-al,3)-Glc" are used interchangeably.

The term "cultivation" refers to the culture medium wherein the cell is cultivated or fermented, the cell itself, and the saccharide(s) that is/are produced by the cell in whole broth, i.e. inside (intracellularly) as well as outside (extracellularly) of the cell.

Brief description of the drawings

The following drawings will serve as further illustration and clarification of the present invention and are not intended to be limiting in any way.

Figure 1. Litters were tested for Cryptosporidium spp. at weaning day (WO). There were 18 litters from which pigs were selected (L1-L18) but only 14 were tested for Cryptosporidium spp. Litters indicated with "*" had no 2'FL-treated pigs that tested positive for Cryptosporidium spp. Litters indicated with "#" had no control pigs that tested positive for Cryptosporidium spp.

Figure 2. Percentage of Cryptosporidium spp.-positive pigs. Pigs were assigned to be treated with 2'FL form 5 days before weaning (WO) till 2 weeks after weaning (i.e. 19 days; W2). The presence of Cryptosporidium spp. was tested in both the 2'FL treated group and the placebo group. A chi-square test was used to compare the treated and placebo groups at the different time-pints. "**" and "***" _re fer to a statistically significant difference between the 2'FL treatment group and placebo group of P < 0.005 and P < 0.001, respectively. W1 = 1 week after weaning; W2 = 2 weeks after weaning; W3 = 3 weeks after weaning.

Examples

The invention will be described in more detail in the examples. The following examples will serve as further illustration and clarification of the present invention and are not intended to be limiting in any way.

Example 1: 2'FL

2'-fucosyllactose (2'FL) was recombinantly produced in E. coli and purified as described in examples 10, 13 and 14 of WO 2022/034079, and subsequently spray dried as described in Example 21 of WO 2022/034079 to obtain 2"FL powder (purity 89.6 %).

Example 2: Cryptosporidium spp. infection in pigs

Study design

The experiment was organized in two periods: pre-weaning and post-weaning, on 144 piglets, equally gender distributed.

During the first period of the experiment (pre-weaning), the progeny of 18 sows and one boar from one weaning round was used. This ensured that the genetic background of the control and treated piglets was similar. Thirteen days before weaning, piglets were weighed (average weight of about 5.0 kg) to divide the pigs of one litter evenly over a control group and a test group. All piglets still stayed with and sucked their mothers.

For five continuous days until the day of weaning, test pigs received 5 ml of 2'-fucosyllactose (2'FL) solution orally (drenching). This solution was made by adding 111.6 g 2'FL (89.6% purity; see Example 1) in 1 L of physiological saline to make a final concentration of 100 g/l 2'FL. Hence, the daily dose was 0.5 g per pig. Control piglets received 5 ml of physiological saline with a syringe, to keep the stress level due to drenching equal between both groups.

The second period of the experiment started at weaning day (W0) and lasted for 3 weeks (W3). At weaning, the piglets (average weight of about 9.0 kg) of 18 litters were distributed over 24 pens: 6 pens of 6 gilts and 6 pens of 6 castrated male piglets per treatment group (12 pens of the placebo group and 12 pens of the 2'FL-treated group). From weaning, test pigs received the test component (2'FL) via the feed at the concentration of 0.2% (2.23 g 2'FL (89.6% purity) per kg feed) for two more weeks in the weaning diet. Control pigs (placebo group) received the same feed but lacking the test component (2'FL). Piglets had free access to feed lot (ad libitum). Based on the feed intake measurement, piglets consumed between 300 g to 350 g feed per day during the first two weeks after weaning, i.e. the daily dose of 2'FL supplementation in feed (test pigs) was between 0.6 g to 0.7 g per pig. Diets

For two weeks from weaning, piglets received ad libitum weaning diet (placebo group) or weaning diet supplemented with 0.2% 2'FL (treated group). From two weeks after weaning, all piglets received the same prestarter diet (i.e. the prestarter diet for the placebo group and for the treated group are identical, i.e. not supplemented with 2'FL). Ingredient composition of weaning and prestarter diets are presented in table 1.

Table 1. Ingredient composition (%) of the weaning and prestarter diet

* The premix contained 80% dairy products and 20% vitamin and mineral premix, providing the following quantities of vitamins and minerals per kilogram of diet: 15,000 III vitamin A, 2,000 III vitamin D3, 100 mg vitamin E, 2 mg vitamin K, 2.5 mg vitamin Bl, 7.5 mg vitamin B2, 20 mg vitamin B5, 5 mg vitamin B6, 0.04 mg vitamin B12, 100 mg vitamin C, 30 mg niacin, 324 mg choline, 3 mg folic acid, 0.15 mg biotin, 516 mg Ca, 419 mg P, 165 mg Mg, 353 mg Na, 1,375 mg Cl, 1,227 mg K, 234 mg S, 100 mg Fe, 160 mg Cu, 60 mg Mn, 100 mg Zn, 2 mg I, and 0.4 mg Se.

Detection of Cryptosporidium in faeces

Faecal samples were collected directly from the recta of all piglets at weaning day (W0), 1 (Wl), 2 (W2) and 3 weeks (W3) post-weaning. The fresh samples were stored on ice during collection in the barn and aliquoted into small vials to be stored at -80°C. Cryptosporidium antigen was tested from 100 mg faeces of three animals out of six per pen (50% of population) using Cryptosporidium Monoscreen Ag ELISA kit from Bio-X Diagnostics S.A. (Rochefort, Belgium). The result was justified as positive or negative with the presence of Cryptosporidium antigen as compared to the positive control involved in the kit as instructed by the manufacturer. At each time point, comparisons between placebo and treated were performed based on Chi-square test.

Results

At weaning day, piglets were deprived from their mothers and litter mates to be divided into different pens in the way that the gender and 2'FL treatment were taken into account. Faeces of certain piglets from 14 out of 18 litters were tested for the presence of Cryptosporidium spp. Figure 1 depicts the number of control or 2'FL-treated pigs that are positive or negative with Cryptosporidium. Out of 14 tested litters, only two were negative for the pathogen (Lil and L18). At least one control pig from ten litters shed Cryptosporidium in their faeces while that of 2'FL-treated were present in eight litters. It means that Cryptosporidium infection had happened during suckling period.

Out of 70 tested animals at weaning day (W0), 25.7% tested pigs in the placebo group were positive for Cryptosporidium (18 out of 70 pigs) while there were only 14.3% were positive in the 2'FL-treated group (10 out of 70 pigs) (P-value = 0.0509) (Fig. 2). The result indicates that after five days treatment with 2'FL orally, those piglets got less infected by Cryptosporidium than the control group. One week post-weaning, 20.6% and 5.9% piglets were positive in the placebo and 2'FL-treated group, respectively. The difference was significantly (P-value = 0.0038). Two weeks post weaning, only one pig out of 71 was positive (1.4%) in the 2'FL-treated group while 16.9% of the pigs were positive in the placebo group (P-value = 0.000722). Three weeks post weaning, only one pig out of 71 was positive (1.4%) in the 2'FL-treated group while 7% of the pigs were positive in the placebo group (P-value = 0.095).

2'FL appears to greatly reduce the incidence of Cryptosporidium infection upon a treatment of five days with 2'FL and the Cryptosporidium infection was almost cleared after 19 days of treatment. In contrast, the Cryptosporidium infection was not cleared in control pigs, not even after 26 days. In conclusion, 2'FL treatment reduced the infection of Cryptosporidium in pigs and it also enhanced the clearance of the infection. List of references

Caccio and Widmer (2014), Cryptosporidium: parasite and disease, Springer.

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Dumon et al (2001), In vivo fucosylatoin of lacto-N-neotetraose and lacto-N-neohexaose by heterologous expression of Helicobacter pylori alpha-1,3 fucoysltransferase in engineered Escherichia coli, gloconj. J. 18(6): p. 465-474.

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Robertson et al (2014), Cryptosporidiosis in farmed animals. In: Caccio S, Widmer G., editors, Cryptosporidium: parasite and disease, Springer 2014, p. 149-235.

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- W02020/115671

- WO2021/067641

- WO2021/242866

- W02022/034073

- WO 2022/034075

- WO 2022/034077

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