A preventative HIV-1
vaccine is an essential intervention needed to halt the HIV-1 pandemic.
Neutralizing antibodies protect against HIV-1
infection in animal models, and thus an approach toward a protective HIV-1
vaccine is to induce broadly cross-reactive
neutralizing antibodies (
bnAbs). One strategy to achieve this goal is to define envelope (Env) evolution that drives
bnAb development in
infection and to recreate those events by vaccination. In this study, we report the immunogenicity, safety, and efficacy in rhesus macaques of an SIV-based
integrase defective lentiviral vector (IDLV) expressing sequential
gp140 Env immunogens derived from the CH505 HIV-1-infected individual who made the CH103 and CH235
bnAb lineages. Immunization with IDLV expressing sequential CH505 Envs induced higher magnitude and more durable binding and
neutralizing antibody responses compared to
protein or DNA +/- protein immunizations using the same sequential envelopes. Compared to monkeys immunized with a vector expressing Envs alone, those immunized with the combination of IDLV expressing Env and CH505
Env protein demonstrated improved durability of antibody responses at six months after the last immunization as well as lower peak
viremia and better virus control following autologous SHIV-CH505 challenge. There was no evidence of vector mobilization or recombination in the immunized and challenged monkeys. Although the tested
vaccines failed to induce
bnAbs and to mediate significant protection following SHIV-challenge, our results show that IDLV proved safe and successful at inducing higher titer and more durable immune responses compared to other
vaccine platforms.