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.

描述：迄今为止，尚无疫苗策略成功地诱导了针对HIV-1的广泛中和抗体（BNAB）。体外分析，RV144疫苗效率试验中的被动抗体转移研究和抗体反应的分析表明，非中和抗体可能有助于保护HIV-1传播。 HIV-1 Env MPER，V2和V3中的三个线性区域已被实施，作为受保护的非中和抗体的潜在靶标。我们已经构建了一种新型的重组乳杆菌嗜酸疫霉疫苗平台，该平台已口服，并诱导插入细菌表面层蛋白中的MPER PEPPEIDES抗原特异性粘膜IgA和全身IgG。我们已经开发了两个不同的调节器，用于与嗜酸乳杆菌，IL1。和鞭毛蛋白（FLIC）一起使用。特定目标1将确定特定目标2将测试表达候选MPER，V2和/或V3表位的重组乳杆菌是否可以诱导粘膜和全身性抗体反应，这些抗体和全身性抗体反应受到HLA-DR Transgenic（Drag），人性小鼠模型的阴道HIV-HIV-1挑战。