Comparative mucosal immunogenicity of HIV gp41 membrane-proximal external region (MPER) containing single and multiple repeats of ELDKWA sequence with defensin peptides

The MPER of gp41 of HIV-1 has received great attention and is widely recognized as a promising target for the development of AIDS vaccine. We investigated the ability of trirepeat of ELDKWA sequence of gp41 antigen with defensins in liposome using multiple-shot immunization strategy in the mice model. The designed was used to enhance the immunogenicity and exposure of MPER in its native conformation for the induction of MPER-specific HIV-1 neutralizing antibodies. To characterize, we estimated the antibody levels (IgG/IgA) in serum as well as in lung, intestinal, vaginal and rectal washes till day 120 in outbred and inbred (H-2(b) and H-2(d)) mice using liposome as delivery vehicle. The representative sera and washes were also tested for in vitro neutralization with CCR5-tropic Indian HIV-1 primary isolates. We observed that the modified HIV antigen containing trirepeat of ELDKWA with defensins was showing significantly (p<0.001) higher IgG/IgA antibody titre (102,400-204,800) in sera as well as in different mucosal washes (1600-6400) than standard HIV-1 antigen. Furthermore, sera from the modified HIV-1 antigen with defensins found to exhibit higher neutralizing activities (ranging from 59.3% to 84.6%) than the standard HIV-1 antigen. These results show that the induction of MPER-specific HIV-1 neutralizing antibodies could be achieved through a rationally designed vaccine strategy.