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Oral Induction of Mucosal and Systemic Antibodies Against HIV-1 gp41 MPER

口服诱导抗 HIV-1 gp41 MPER 的粘膜和全身抗体

基本信息

批准号：
8892070
负责人：
Gregg A Dean
金额：
$ 18.59万
依托单位：
COLORADO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-01 至 2017-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8892070
关键词：
Address Adjuvant Antibodies Antibody Response Antigens B-Lymphocytes Binding Data Epithelium Epitopes Flagellin HIV HIV Envelope Protein gp41 HIV-1 HLA-DR Antigens Health Human Immune Immune response Immune system Immunization Immunoglobulin A Immunoglobulin Class Switching Immunoglobulin G In Vitro Infection Interleukin-1 Intestines Knockout Mice Lactobacillus acidophilus Membrane Modeling Mucosal Immunity Mucous Membrane Mucous body substance Mus Nature Oral Oral mucous membrane structure Organism Passive Transfer of Immunity Peptides Polymeric Immunoglobulin Receptors Probiotics Proteins Recombinants Risk Route Salmonella Serum Sexual Transmission Side Surface T cell response T-Lymphocyte TNFSF5 gene Testing Transgenic Organisms Vaccination Vaccine Design Vaccines Vagina Virus base efficacy trial gp160 interest mouse model mucosal vaccination mucosal vaccine neutralizing antibody novel response transmission process vaccination strategy vaccine efficacy vaccine evaluation

项目摘要

DESCRIPTION: To date, no vaccine strategy has successfully induced potent broadly neutralizing antibodies (BnAb) against HIV-1. In vitro analysis, passive antibody transfer studies and analysis of antibody responses in the RV144 vaccine efficacy trial suggest non- neutralizing antibodies might contribute to protection against HIV-1 transmission. Three linear regions in the HIV-1 Env MPER, V2 and V3 have been implicated as potential targets of protective non-neutralizing antibody. We have constructed a novel recombinant Lactobacillus acidophilus vaccine platform that is orally delivered and induces antigen-specific mucosal IgA and systemic IgG against MPER peptides inserted into the bacterial surface layer protein. We have developed two different adjuvants for use with recombinant L. acidophilus, IL1� and flagellin (FliC). Specifi Aim 1 will determine the optimal adjuvant for mucosal immunization and whether responses are T-cell dependent or independent. Specific Aim 2 will test whether recombinant Lactobacillus acidophilus expressing candidate MPER, V2, and/or V3 epitopes can induce mucosal and systemic antibody responses that are protective against vaginal HIV-1 challenge in the HLA-DR transgenic (DRAG), humanized mouse model.

迄今为止，还没有一种疫苗策略能够成功诱导针对HIV-1的强效广泛中和抗体（BnAb）。体外分析、被动抗体转移研究和RV144疫苗疗效试验中抗体反应分析表明，非中和抗体可能有助于防止HIV-1传播。HIV-1 Env MPER中的三个线性区域，V2和V3被认为是保护性非中和抗体的潜在靶点。我们构建了一种新的重组嗜酸乳杆菌疫苗平台，该平台可以口服给药，并诱导抗原特异性粘膜IgA和全身IgG对抗插入细菌表层蛋白的MPER肽。我们已经开发了两种不同的佐剂用于重组嗜酸乳杆菌，il - 1和鞭毛蛋白（FliC）。特异性Aim 1将决定粘膜免疫的最佳佐剂，以及反应是t细胞依赖还是独立的。在HLA-DR转基因（DRAG）人源化小鼠模型中，Specific Aim 2将测试表达候选MPER、V2和/或V3表位的重组嗜酸乳杆菌是否能诱导粘膜和全身抗体反应，从而对阴道HIV-1攻击起到保护作用。