Abstract
Anti-p17 antibodies are able to neutralize human immunodeficiency virus (HIV) entry in a mouse model. In this study, we identified a region of sequence similarity between the epitopes of anti-p17 neutralizing antibodies and anti-gp41 neutralizing 2F5 antibody and verified cross-reactivity between p17 and 2F5 in vitro. The p17 sequence was modified to increase sequence identity between the p17 and 2F5 epitopes, which resulted in enhanced cross-reactivity in vitro. Immunogenicity of wild-type and modified p17 was characterized in a rabbit model. Both wild-type and mutated p17 induced anti-gp41 responses in rabbits; sera from these animals reacted with gp41 from different HIV clades. Moreover, introduction of the 2F5 sequence in p17 resulted in induction of antibodies with partially neutralizing activity. Based upon these data, we suggest that the natural cross-reactivity between HIV-1 p17 protein and 2F5 antibody can be exploited to induce antibodies with neutralizing activity in an animal model.
Highlights
Despite the high variability of human immunodeficiency virus (HIV), approximately 15–30% of infected patients develop broadly neutralizing antibodies able to neutralize entry of the majority of HIV strains [1,2,3]
We demonstrated that the gp41-specific 2F5 bnAb cross-reacted with the p17 Gag subunit
We found that introduction of the full-length 2F5 epitope in p17 increased this cross-reactivity in vitro
Summary
Despite the high variability of human immunodeficiency virus (HIV), approximately 15–30% of infected patients develop broadly neutralizing antibodies (bnAbs) able to neutralize entry of the majority of HIV strains [1,2,3]. Current vaccine strategies have not yet been able to induce high bnAbs titers [13] Another important target for HIV vaccination is the Gag polyprotein. The p17 sequence, ELDKWRK, is part of the epitope of an anti-p17 antibody that neutralizes HIV entry [22], and a bnAb, 2F5, directed against the HIV gp envelope subunit, was identified in an infected individual [23, 24]. This 2F5 antibody recognizes an epitope with the sequence ELDKWAS in the membrane proximal external region (MPER) of gp41 [24]. Preliminary immunization experiments in an animal model confirmed the ability of p17 to induce anti-gp immune responses with neutralizing activities, which are improved by mutating p17
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call