Improved induction of antibodies against key neutralizing epitopes by HIV-1 gp120 DNA prime-protein boost vaccination compared to gp120 protein only vaccination

A major challenge in HIV-1 vaccine development is to elicit potent and broadly neutralizing antibodies effective against primary viral isolates. Previously, we showed that DNA prime-protein boost vaccination using HIV-1 gp120 antigens was more effective in eliciting neutralizing antibodies against primary HIV-1 isolates compared to a recombinant gp120 protein only vaccination approach. In the current study, we analyzed the difference of antibody specificities in rabbit sera elicited by these two immunization regimens using peptide ELISA and a competitive virus capture assay. Our results indicate that a DNA prime-protein boost regimen is more effective than a protein alone vaccination approach in inducing antibodies that target two key neutralizing domains: the V3 loop and CD4 binding site. In particular, positive antibodies targeting several peptides that overlap with the known CD4 binding area were only detected in DNA primed sera. Different profiles of antibody specificities provide insight into the mechanisms behind the elicitation of better neutralizing antibodies with the DNA prime-protein boost approach and our results support the use of this approach to further optimize Env formulations for HIV vaccine development