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

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已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 β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。

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.