Bridging Antibody Fc-mediated Antiviral Functions Across Humans and Non-human Primates

桥接抗体 Fc 介导的人类和非人类灵长类动物的抗病毒功能

• 批准号: 9925737
• 负责人: GEORGIA Doris TOMARAS
• 金额: $ 410.48万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9925737
• 关键词: Animal Model; Animals; Antibodies; Antigen-Antibody Complex; Antiviral Agents; Biology; Biophysics; Cells; Chemicals; Clinic; Clinical Trials; Collaborations; Communication; Effector Cell; Ensure; Epitopes; Expression Profiling; Fc Receptor; Fc domain; Financial Activity; Genotype; Goals; Grant; HIV; HIV vaccine; HIV-1; HIV-1 vaccine; Human; Human immunodeficiency virus test; Immune system; Immunity; Infection prevention; Institutes; Institution; Intervention; Learning; Macaca mulatta; Maps; Mediating; Memory; Modeling; Monitor; Monoclonal Antibodies; Outcome; Passive Immunization; Phenotype; Positioning Attribute; Prevention strategy; Recording of previous events; Regimen; Research Personnel; Resources; Rhesus; Risk; Role; Specificity; Structure; Supervision; Testing; Translating; Translations; Vaccine Design; Vaccines; Virion; Virus; Work; antigen binding; base; design; efficacy trial; experience; glycosylation; immunoprophylaxis; improved; insight; nonhuman primate; programs; public health relevance; receptor function; recruit; response; success; synergism; tool; translation to humans; vaccine development; vaccine trial

 DESCRIPTION (provided by applicant): HIV-1 vaccine efficacy trials and multiple animal studies, including those related to HIV-cure strategies, have shown that antibody interactions with cells - mediated by the antibody constant (Fc) region - can harness multiple aspects of the immune system to provide protection through mechanisms other than by neutralization. However, it is unknown whether candidate HIV-1 vaccine regimens that include induction of Fc-mediated antibody functions can be tested in the rhesus macaque (RM) nonhuman primate (NHP) in a way that can be translated to humans. In order to more effectively translate insights gained from RM studies to the clinic, there is a need to fully define the protective signatures of Fc-mediated antibody functions across rhesus macaques and humans. The work we propose will map antibody (Ab) and Fc-receptor (FcR) biology across humans and RMs with the goal of making observed protective responses in RMs more predictive of human responses, thus accelerating the most promising vaccine concepts to be advanced to the clinic with success. Our central hypothesis is that the RM model can be substantially improved for testing antibody-based interventions and vaccines through elucidation of key variables that impact species-specific FcγR-dependent effector functions (i.e. antibody epitope specificity, immune complex formation, isotype/subclass, glycosylation, and FcR genotype/phenotype). To test this, we propose three synergistic, inter-related scientific Projects supported by three Cores to achieve the following Overall Aims: Overall AIM 1. Characterize effective anti-HIV-1 Fc-FcR biology across RM to humans. Overall AIM 2. Define HIV-1 virion and infected cell epitopes for antibody recognition. Overall AIM 3. Determine the Fv and Fc features of antibodies yielding maximal anti-HIV-1 activity.



项目成果

Coming together at the hinges: Therapeutic prospects of IgG3.

• DOI: 10.1080/19420862.2021.1882028
• 发表时间: 2021-01
• 期刊: mAbs
• 影响因子: 5.3
• 作者: Chu TH;Patz EF Jr;Ackerman ME
• 通讯作者: Ackerman ME

Adjuvanted HIV-1 vaccine promotes antibody-dependent phagocytic responses and protects against heterologous SHIV challenge.

• DOI: 10.1371/journal.ppat.1008764
• 发表时间: 2020-09
• 期刊: PLoS pathogens
• 影响因子: 6.7
• 作者: Om K;Paquin-Proulx D;Montero M;Peachman K;Shen X;Wieczorek L;Beck Z;Weiner JA;Kim D;Li Y;Mdluli T;Shubin Z;Bryant C;Sharma V;Tokarev A;Dawson P;White Y;Appelbe O;Klatt NR;Tovanabutra S;Estes JD;Matyas GR;Ferrari G;Alving CR;Tomaras GD;Ackerman ME;Michael NL;Robb ML;Polonis V;Rolland M;Eller MA;Rao M;Bolton DL
• 通讯作者: Bolton DL

Recent insights into Fc-mediated effector responses to HIV-1.

• DOI: 10.1097/coh.0000000000000638
• 发表时间: 2020-09
• 期刊: Current opinion in HIV and AIDS
• 影响因子: 4.1
• 作者: Carpenter MC;Ackerman ME
• 通讯作者: Ackerman ME