Glycoantigen evolution targeting antibodies of the PGT 128 lineage

糖抗原进化靶向 PGT 128 谱系抗体

• 批准号: 10062844
• 负责人: Isaac Jonathan Krauss
• 金额: $ 56.08万
• 依托单位: BRANDEIS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2022-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10062844
• 关键词: Affinity; Amino Acids; Animal Model; Antibodies; Antibody Response; Antigens; Award; B cell repertoire; B-Lymphocytes; Binding; Biophysics; Cell Culture Techniques; Cells; Collaborations; Complex; Directed Molecular Evolution; Elements; Epitopes; Evaluation; Event; Evolution; Glycopeptides; Goals; HIV; HIV Envelope Protein gp120; HIV Infections; Health; Human; Hybridomas; Immune response; Immunization; Individual; Infection; Knock-in; Knock-in Mouse; Libraries; Macaca mulatta; Mannose; Messenger RNA; Methods; Monitor; Monoclonal Antibodies; Mus; Oryctolagus cuniculus; Patients; Peptides; Phase; Polysaccharides; Protocols documentation; Regimen; Site; Specificity; Structure; Surface; Techniques; Testing; Vaccines; Variant; Viral; Virus; cohort; deep sequencing; design; experimental study; immunogenicity; neutralizing antibody; polypeptide; reconstitution; response; scaffold; tool; vaccine development

Project Summary/Abstract Extensive study of HIV+ individuals in recent years has brought to light many examples of antibodies that can neutralize a broad range of HIV strains and protect against viral challenge in animal models of infection. The portion of viral surface most commonly targeted by such antibodies is now known to be the “high-mannose patch”: among patients producing broadly-neutralizing antibodies, 38% target this one region of the virus. One of the most potent high mannose patch antibodies, PGT128, binds to a particular arrangement of high-mannose glycans and conserved peptide residues. Our goal is to develop vaccine immunogens which mimic this arrangement precisely and be used to elicit PGT128-like antibodies. Our approach will utilize unique directed evolution methods to develop glycoimmunogens in which PGT128 epitope elements are correctly reconstituted. It is also possible that additional immunogens will be required to correctly prime the immune response by stimulating germline precursors of PGT128. Therefore, we will develop glycopeptides targeting both mature and germline PGT128 antibodies. In collaboration with David Nemazee at Scripps, we will investigate the ability of these glycopeptides in combination, to activate a germline PGT128 response that can mature into a response with broadly- neutralizing PGT128-like specificity.

项目总结/文摘