Cleaved, stabilized HIV-1 Env trimers for structural and vaccine studies

用于结构和疫苗研究的裂解、稳定的 HIV-1 包膜三聚体

• 批准号: 10427129
• 负责人: JOHN P MOORE
• 金额: $ 414.99万
• 依托单位: WEILL MEDICAL COLL OF CORNELL UNIV
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10427129
• 关键词: Academic Medical Centers; Amino Acid Substitution; Animals; Antibodies; Antibody Response; Antigens; Autologous; Binding; Biophysics; Cells; Clinical Trials; Collaborations; Communication; Complex; Cryoelectron Microscopy; Data; Development; Doctor of Philosophy; Electron Microscopy; Epitopes; Foundations; Funding; Generations; Genotype; Glycoproteins; Goals; HIV Envelope Protein gp120; HIV-1; HIV-1 vaccine; Human; Hydrogen; Immune system; Infection; Letters; Macaca; Mass Spectrum Analysis; Mediating; Negative Staining; Oryctolagus cuniculus; Outcome; Principal Investigator; Procedures; Process; Production; Property; Proteins; Reagent; Recombinant Proteins; Recombinants; Regulation; Research; Research Institute; Research Project Grants; Resolution; Respiratory Syncytial Virus Vaccines; Roentgen Rays; Scientist; Shapes; Structure; Surface; Testing; Uncertainty; United States National Institutes of Health; Vaccine Research; Vaccines; Viral; Virion; Virus; Work; X-Ray Crystallography; base; biophysical analysis; biophysical techniques; design; flexibility; immunogenicity; improved; insight; iron oxide nanoparticle; medical schools; milligram; neutralizing antibody; prevent; programs; prophylactic; prototype; response; stable cell line; trimer core; vaccine development; vaccine trial; ward

Overall Abstract This HIVRAD Program Project renewal application is made in response to PAR-18-319. It contains two Research Projects, one Scientific Core and an Administrative Core, under the direction of Principal Investigator, John P. Moore, PhD (Weill Cornell Medical College; WCMC) and co-Principal Investigator, Ian A. Wilson, PhD (The Scripps Research Institute; TSRI). The goal of the project is to further develop stable, soluble, cleaved trimeric mimics of the native Env spike (SOSIP trimers) as antigens for structural studies and as immunogens for the development of vaccines aimed at inducing broadly neutralizing antibodies (bNAbs). Our central hypothesis is that a proteolytically cleaved, soluble, trimeric form of HIV-1 Env is an appropriate structural antigen for high resolution x-ray crystallography and electron microscopy studies, and a suitable immunogen for vaccine research aimed at the induction of bNAbs. Our intent is to use structure-based information to help develop an effective, prophylactic HIV-1 vaccine (or component of a more complex vaccine) that is based on the concept of inducing sufficient titers of bNAbs. We believe that one way to accomplish this goal is to make soluble recombinant protein mimics of the native, trimeric Env spike that is present on virions, that mediates virus entry into cells and that is the target for all known bNAbs. SOSIP trimers have the desired properties and can be produced efficiently, including in the amounts and qualities required for human clinical trials. This HIVRAD project team has made excellent progress during the past 4 years, and now seeks support to continue to work together. Its research plan involves the following sub-components. Project 1: John P. Moore (and Rogier W. Sanders): Design of SOSIP trimers Project 2: Ian A. Wilson (and Andrew B. Ward): Structural studies of SOSIP trimers Core B: PJ Klasse: Production of SOSIP trimers Core A: John P. Moore: Administrative support Rogier W. Sanders of the Amsterdam University Medical Centers, Amsterdam will direct a sub-component of Project 1. Andrew B. Ward of The Scripps Research Institute will be the co-leader of Project 2. As well as the integral components of the HIVRAD team, we propose to maintain and expand an extensive network of research collaborations, and we will continue to provide SOSIP trimers and related reagents to the many scientists who request our support.

整体的抽象