Title:
ENGINEERED OUTER DOMAIN (EOD) OF HIV GP120, MUTANTS AND USE THEREOF
Document Type and Number:
WIPO Patent Application WO/2016/205704
Kind Code:
A3
Abstract:
The present invention relates to engineered outer domain (eOD) immunogens of HIV gp120 and mutants thereof and methods of making and using the same. The present invention also includes fusions of eOD to various protein multimers to enhance immunogenicity. The mutant eODs bind to neutralizing antibody precursors. The mutant eODs can activate germline precursors on the pathway to eliciting a broadly neutralizing antibody (bnAb) response. The invention also relates to immunized knock-in mice expressing germline-reverted heavy chains. Induced antibodies showed characteristics of bnAbs and mutations that favored binding to near-native HIV-1 gp120 constructs. In contrast, native-like immunogens failed to activate precursors. The invention also relates to rational epitope design that can prime rare B cell precursors for affinity maturation to desired targets.
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Inventors:
SCHIEF WILLIAM (US)
MENIS SERGEY (US)
KULP DANIEL (US)
JARDINE JOSEPH (US)
MENIS SERGEY (US)
KULP DANIEL (US)
JARDINE JOSEPH (US)
Application Number:
PCT/US2016/038162
Publication Date:
March 16, 2017
Filing Date:
June 17, 2016
Export Citation:
Assignee:
INT AIDS VACCINE INITIATIVE (US)
SCRIPPS RESEARCH INST (US)
SCRIPPS RESEARCH INST (US)
International Classes:
A61K39/21; A61K38/00; C07K14/005
Foreign References:
| US20140322269A1 | 2014-10-30 | |||
| US20120282264A1 | 2012-11-08 | |||
| US20110217338A1 | 2011-09-08 | |||
| US20140302081A1 | 2014-10-09 |
Other References:
JARDINE ET AL.: "HIV-1 broadly neutralizing antibody precursor B cells revealed by germline-targeting immunogen", SCIENCE, vol. 351, 25 March 2016 (2016-03-25), pages 1458 - 1463, XP055367348
AZOITEI ET AL.: "Computational design of protein antigens that interact with the CDR H3 loop of HIV broadly neutralizing antibody 2F5", PROTEINS, vol. 82, no. 10, October 2014 (2014-10-01), pages 2770 - 2782, XP055367355
AZOITEI ET AL.: "Computational design of protein antigens that interact with the CDR H3 loop of HIV broadly neutralizing antibody 2F5", PROTEINS, vol. 82, no. 10, October 2014 (2014-10-01), pages 2770 - 2782, XP055367355
Attorney, Agent or Firm:
KOWALSKI, Thomas J. (US)
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