Monoclonal antibody isolation and characterization

单克隆抗体分离和表征

• 批准号: 10930466
• 负责人: Rosemarie Mason
• 金额: $ 118.66万
• 依托单位: NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10930466
• 关键词: Animals; Antibodies; Antibody Therapy; Antigens; Chimeric Proteins; Development; Epitope Mapping; Glycoproteins; HIV; HIV-1; Henipavirus; Human; Immunize; Individual; Intervention; Link; Macaca mulatta; Messenger RNA; Methods; Monoclonal Antibodies; Nipah Virus; Peripheral Blood Mononuclear Cell; Prevention; Rhesus; Sampling; Testing; Vaccination; Virus; Virus Diseases; clinically relevant; neutralizing antibody; pathogen; pathogenic virus; prevent; screening; single cell technology

We are isolating HIV-specific antibodies (Abs) from rhesus macaques that were protected against repeated HIV challenge following heterologous prime-boost vaccination with mRNA expressing HIV immunogens. We have isolated 2 HIV-neutralizing Abs from the first animal screened and are screening these Abs for neutralization breadth against our 208 HIV-1 virus panel. For Nipah virus antibody discovery, we are isolating NiV-specific mAbs from rhesus macaques immunized with NiV glycoprotein (G) or fusion (F) protein, and from human peripheral blood mononuclear cell (PBMC) samples from VRC322 study in which individuals received prime-boost vaccination with mRNA-1215 expressing secreted pre-fusion stabilized NiV fusion (F) protein covalently linked to NiV glycoprotein (G). So far we have isolated more than 70 rhesus-derived and 10 human-derived NiV-specific neutralizing Abs which are being characterized for neutralization potency, cross-neutralization of related henipaviruses and epitope mapping.

我们正在从恒河猴中分离HIV特异性抗体（Abs），这些恒河猴在用表达HIV免疫原的mRNA进行异源初免-加强免疫接种后受到保护，免受反复的HIV攻击。我们已经从筛选的第一只动物中分离出2种HIV中和抗体，并正在筛选这些抗体对我们的208种HIV-1病毒组的中和宽度。 对于尼帕病毒抗体发现，我们从用NiV糖蛋白（G）或融合（F）蛋白免疫的恒河猴和来自VRC 322研究的人外周血单核细胞（PBMC）样品中分离NiV特异性mAb，在VRC 322研究中，个体接受了用表达与NiV糖蛋白（G）共价连接的分泌的融合前稳定的NiV融合（F）蛋白的mRNA-1215进行的初免-加强疫苗接种。到目前为止，我们已经分离出超过70种恒河猴衍生的和10种人源的NiV特异性中和Ab，其正在表征中和效力、相关亨尼帕病毒的交叉中和和表位作图。

项目成果

Parsimonious Determination of the Optimal Infectious Dose of a Pathogen for Nonhuman Primate Models.

• DOI: 10.1371/journal.ppat.1005100
• 发表时间: 2015-08
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Roederer M