Induction of bnAbs against HIV-1 gp41.

针对 HIV-1 gp41 的 bnAb 的诱导。

• 批准号: 10603692
• 负责人: Michael W Cho
• 金额: $ 29.73万
• 依托单位: NEOVAXSYN, INC.
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10603692
• 关键词: AIDS Vaccines; AIDS vaccine development; Acquired Immunodeficiency Syndrome; Affinity; Amino Acids; Anti-Retroviral Agents; Antibodies; Antibody Response; Antigen-Antibody Complex; Antigens; B-Lymphocytes; C-terminal; Cells; Cellular Membrane; Chimeric Proteins; Complex; Crystallization; Development; Epitopes; Evaluation; Face; Feasibility Studies; Genes; Goals; Government; HIV-1; Human; Immune system; Immunize; Immunologics; Infection; Iowa; Lead; Length; Membrane; Molecular Conformation; Monoclonal Antibodies; Mus; NF1 gene; Patients; Peptide antibodies; Peptides; Persons; Pharmaceutical Preparations; Phase; Research Proposals; Scaffolding Protein; Side; Small Business Innovation Research Grant; Structure; Surface; Testing; Training; Transgenic Mice; Universities; Vaccines; Vaccinia virus; Variant; Viral; Virus; alpha helix; commercialization; flexibility; gp160; innovation; nanomolar; neutralizing antibody; neutralizing monoclonal antibodies; new technology; novel; novel vaccines; pandemic disease; phase 1 study; prevent; synergism; vaccine candidate; vaccine strategy

PROJECT SUMMARY/ABSTRACT Despite the availability of effective anti-retroviral drugs, there are still about 38 million people living with HIV-1 infection and about 1.5 million people became newly infected just in 2020. A vaccine is critically needed to stop the AIDS pandemic. Induction of broadly neutralizing antibodies (bnAbs) against HIV-1 is the utmost critical goal towards the development of a protective AIDS vaccine. In this R43 Phase I SBIR proposal, we will evaluate a novel “Antibody- Stabilized, Epitope Presentation” (ASEP) vaccine strategy to elicit 10E8-like bnAbs against HIV-1. 10E8, a bnAb isolated from an HIV-1-infected patient that targets the membrane proximal external region (MPER) of HIV-1 gp41, has been shown to neutralize ~98% of all HIV-1 isolates tested. Developing immunogens and/or establishing vaccine strategies that can induce 10E8-like bnAbs would be a major milestone towards AIDS vaccine development. Thus, our proposal is highly significant and, if successful, this project will have great impact in the AIDS vaccine field and immunogens we generate will be commercially valuable. The major innovation and the focus of this proposal is our ASEP vaccine strategy, in which precisely defined immune complexes are used as immunogens. This proposal is founded on three scientific premises. (1) A vaccine that can induce high titers of 10E8-like bnAbs will be protective against HIV-1 infections. (2) Although short peptides are good for focusing antibody responses, they are not ideal B-cell immunogens because they are highly flexible and can exist in many different conformations. (3) The conformation of a peptide can be fixed into a rigid structure when it is bound to an antibody. The primary objective of this Phase I R43 feasibility study is to demonstrate MPER/Antibody immune complexes can be used to elicit 10E8-like bnAbs against HIV-1. Successful completion of this study would overcome a critical roadblock towards development of a protective AIDS vaccine.

项目总结/文摘