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.
Sexual transmission is the primary means by which HIV-1 is spread. Mucosal surfaces are the first point of contact with the virus so a robust immune response at the mucosa may provide protection against infection. We have developed an orally-delivered vaccine based on the probiotic organism, Lactobacillus acidophilus. Our preliminary studies have shown this strategy can induce antibodies at mucosal surfaces and in serum against a highly conserved regions of the HIV-1 envelop. The proposed studies will determine the best approach to induce high levels of long lasting antibody against HIV and will determine whether the response is able to protect humanized mice against challenge.
