Title:
AQUEOUS IMMUNOLOGIC ADJUVANT COMPOSITIONS OF MONOPHOSPHORYL LIPID A
Document Type and Number:
WIPO Patent Application WO2000078353
Kind Code:
A3
Abstract:
An aqueous adjuvant composition comprising an attenuated lipid A derivative and a non-immunostimulatory surfactant or surfactants enhances the immunological response in a warm blooded animal to a protein antigen. Attenuated lipid A derivatives useful according to the subject invention include monophosphoryl lipid A and 3-O-deacylated monophosphoryl lipid A. A surfactant or mixtures of surfactants are dissolved in a solvent. 1,2 Dipalmitoyl-sn-glycero-3-phosphocholine is a preferred surfactant. The dissolved surfactant is added to an attenuated lipid A derivative to obtain a mixture. The molar ratio of attenuated lipid A derivative to surfactant in the mixture is about 4:1. The solvent is evaporated and water is added to the resulting film. The suspension is sonicated in a 60 DEG C water bath until it becomes clear. Animals administered the adjuvant formulation exhibited increased antibody responses to a given antigen as well as displayed enhanced lymphocyte proliferative and cytotoxic T-lymphocyte responses. Intranasal administration of the aqueous adjuvant composition and an antigen stimulates the production of serum and mucosal secreted IgA.
Inventors:
CRANE R THOMAS
Application Number:
PCT/US2000/016384
Publication Date:
March 15, 2001
Filing Date:
June 14, 2000
Export Citation:
Assignee:
CORIXA CORP (US)
International Classes:
A61K9/08; A61K9/00; A61K35/74; A61K39/04; A61K39/08; A61K39/29; A61K39/39; A61K47/10; A61K47/16; A61K47/18; A61K47/36; A61P37/04; C07H13/06; A61K9/127; A61K39/00; (IPC1-7): A61K39/39; A61P37/04
Domestic Patent References:
| WO1998043670A2 | 1998-10-08 | |||
| WO1994021292A1 | 1994-09-29 | |||
| WO1999056776A2 | 1999-11-11 |
Foreign References:
| GB2220211A | 1990-01-04 |
Other References:
S. SASAKI ET AL.: "Monophosphoryl lipid A enhances both humoral and cell-mediated immune responses to DNA vaccination against human immunodeficiency virus type 1.", INFECTION AND IMMUNITY, vol. 65, no. 9, September 1997 (1997-09-01), Washington, DC, USA, pages 3520 - 3528, XP002075736
C. BOECKLER ET AL.: "Immunogenicity of new heterobifunctional cross-linking reagents used in the conjugation of synthetic peptides to liposomes.", JOURNAL OF IMMUNOLOGICAL METHODS, vol. 191, no. 1, 10 May 1996 (1996-05-10), Amsterdam, The Netherlands, pages 1 - 10, XP002075734
A. VERHEUL ET AL.: "Beneficial effects of additional adjuvants on the immune response to haptenated liposomes.", JOURNAL OF LIPOSOME RESEARCH, vol. 6, no. 2, 1996, New York, NY, USA, pages 397 - 414, XP002075735
C. BOECKLER ET AL.: "Immunogenicity of new heterobifunctional cross-linking reagents used in the conjugation of synthetic peptides to liposomes.", JOURNAL OF IMMUNOLOGICAL METHODS, vol. 191, no. 1, 10 May 1996 (1996-05-10), Amsterdam, The Netherlands, pages 1 - 10, XP002075734
A. VERHEUL ET AL.: "Beneficial effects of additional adjuvants on the immune response to haptenated liposomes.", JOURNAL OF LIPOSOME RESEARCH, vol. 6, no. 2, 1996, New York, NY, USA, pages 397 - 414, XP002075735
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