Antigen Design, Production and Vaccine Development

抗原设计、生产和疫苗开发

• 批准号: 8137882
• 负责人: Michael W Cho
• 金额: $ 50.32万
• 依托单位: IOWA STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2013-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8137882
• 关键词: AIDS Vaccines; Antibodies; Antibody Formation; Antigens; B-Lymphocyte Epitopes; Biochemical; Consensus; Consensus Sequence; Epitopes; Generations; Goals; HIV Envelope Protein gp120; HIV-1; Human; Immunology; Membrane; Molecular Biology; Mus; Oryctolagus cuniculus; Peptides; Plague; Production; Property; Protein Biochemistry; Protein Fragment; Proteins; Recombinants; Research Personnel; Vaccines; Virus; base; design; immunogenic; immunogenicity; improved; neutralizing antibody; structural biology; vaccine development; vaccinology; virology

The major objective of the studies being proposed is to design HIV-1 envelope antigens that can elicit broadly reactive neutralizing antibodies (Nabs), with a long-term goal of developing a protective vaccine against the virus. We are taking a two-pronged approach of targeting gp41 membrane proximal external region (MPER) and the outer domain of gp120 (gp120OD). We have generated two prototypic antigens based on soluble form of gp41 MPER and gp1200D derived from M group consensus envelope. Both proteins can elicit Nabs against multiple primary HIV-1 isolates in mice. Our goal is to use current and evolving understanding of biochemical, structural and immunogenic properties of the prototypic antigens to design second-generation antigens that could induce even more potent Nabs. To achieve the goal, we have put together a strong, complementary, collaborative team of investigators with expertise in structural biology, virology, protein biochemistry, molecular biology, immunology and vaccinology. The specific aims of the Project 1 are: (1) to better define B cell epitopes on gp41 MPER, (2) to improve immunogenicity of neutralizing epitopes on gp41 MPER, and (3) to develop and evaluate immunogenicity of antigens based on gp120OD. Successful completion of the proposed studies would represent a major advancement towards developing a protective AIDS vaccine.

提出的研究的主要目的是设计HIV-1包膜抗原，可以引发