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

• 批准号: 8790302
• 负责人: Gregg A Dean
• 金额: $ 22.31万
• 依托单位: COLORADO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8790302
• 关键词: Address; Adjuvant; Antibodies; Antibody Formation; Antigens; B-Lymphocytes; Binding; Data; Epithelium; Epitopes; Flagellin; HIV; HIV Envelope Protein gp41; HIV-1; HLA-DR Antigens; 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; public health relevance; response; transmission process; vaccination strategy; vaccine efficacy; vaccine evaluation

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：到目前为止，没有疫苗策略成功诱导有效的广泛中和抗体（BnAb）抗HIV-1。体外分析、被动抗体转移研究和RV 144疫苗有效性试验中的抗体应答分析表明，非中和抗体可能有助于预防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标。我们已经构建了一种新型的重组嗜酸乳杆菌疫苗平台，其经口递送并诱导针对插入细菌表面层蛋白的MPER肽的抗原特异性粘膜伊加和全身IgG。我们已经开发了两种不同的佐剂用于重组L。嗜酸乳杆菌、IL 1？和鞭毛蛋白（FliC）。Specifi Aim 1将确定用于粘膜免疫的最佳佐剂以及应答是T细胞依赖性的还是非依赖性的。具体目标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可以在HLA-DR转基因（DRAG）人源化小鼠模型中诱导对阴道HIV-1攻击具有保护作用的粘膜和全身抗体应答。