Three different HIV antibodies protected monkeys from acquiring simian-HIV (SHIV) according to a study published in Science Translational Medicine, led by the Vaccine Research Center (VRC) at the National Institute of Allergy and Infectious Diseases (NIAID), which is part of the National Institutes of Health (NIH). The antibodies target the fusion peptide, which is a site on an HIV surface protein that helps the virus fuse with and enter cells.
The NIAID VRC “isolated a fusion peptide-directed human antibody, called VRC34.01, from a person living with HIV who donated blood samples for research. They also isolated two antibodies from rhesus macaques—a species of monkey with immune systems like humans’—who previously had received a vaccine regimen designed to generate fusion peptide-directed antibodies.” The study sought to provide proof-of-concept for human vaccine design that isolates the fusion peptide as a target. SHIV challenge – or “administering an infective dose of SHIV” – to rhesus macaques is “a widely used animal model for assessing the performance of HIV antibodies and vaccines.”
In this study, “rhesus macaques in each of four groups received a single intravenous infection of one” of the three types of antibodies – “a 2.5 or 10 mg/kg of bodyweight dose of VRC34.01, or one of the two vaccine-elicited rhesus macaque antibodies – and other monkeys received a placebo infusion.” Each monkey was then challenged five days after infusion with a strain of SHIV “known to be sensitive to fusion peptide-directed antibodies.”
Each monkey that received a placebo infusion acquired SHIV following the challenge. However, among monkeys that received VRC34.01 infusions, “none receiving the 10 mg/kg dose and 25% of those receiving the 2.5 mg/kg dose acquired SHIV. Of those that received the vaccine-elicited rhesus macaque antibodies, no monkeys receiving the antibody called DFPH-a.15 acquired SHIV, and 25% of those receiving the antibody called DF1W-a.01 acquired SHIV. Over time, the concentration of antibodies in the blood of animals that received DFPH-a.15 declined. Those animals were re-challenged 30 days later to see if the lower concentration of antibodies had a decreased protective effect, and half of them acquired SHIV.” Protection from SHIV was dose dependent, or higher in monkeys with greater concentrations of the antibodies in their blood.
According to the authors of the study, these findings “represent the proof-of-concept that fusion peptide-directed antibodies can provide protection against SHIV and help determine the concentration of antibodies a vaccine would need to generate to be protective.” The findings also support further work in designing preventive HIV vaccines targeting the fusion peptide in humans. The study concludes that the concepts used in this study will need to be expanded by “generating multiple varieties of fusion peptide-directed antibodies” in humans, which would increase the likelihood that a vaccine could prevent against different HIV variants.
NIH’s website has the release.
