By IDSE News Staff
Three different HIV antibodies independently protected monkeys from acquiring simian-HIV (SHIV) in a placebo-controlled proof-of-concept study intended to inform development of a preventive HIV vaccine for humans.
The antibodies—a human broadly neutralizing antibody and two antibodies isolated from previously vaccinated monkeys—target the fusion peptide, a site on an HIV surface protein that helps the virus fuse with and enter cells (Sci Transl Med 2024 Jan 17. doi:10.1126/scitranslmed.adh9039).
Antibodies that target the fusion peptide can neutralize diverse strains of HIV. The Vaccine Research Center (VRC) at the National Institute of Allergy and Infectious Diseases 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 that had received a vaccine regimen designed to generate fusion peptide–directed antibodies.
In this study, rhesus macaques in each of four groups received a single IV infusion of one type of antibody—a 2.5- or 10-mg/kg body-weight dose of VRC34.01, or one of the two vaccine-elicited rhesus macaque antibodies—whereas others received a placebo infusion. To determine the protective effect of the antibodies, each monkey was challenged five days after infusion with a strain of SHIV known to be sensitive to fusion peptide–directed antibodies.
All the monkeys that received placebo acquired SHIV following the challenge. Among monkeys that received the 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 macaque antibodies, none 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 rechallenged 30 days later to see whether the lower concentration of antibodies had a decreased protective effect, and half of them acquired SHIV.
The three antibodies studied each provided statistically significant protection from SHIV, and the effect was dose dependent, according to the researchers.
These findings represent the proof of concept that fusion peptide–directed antibodies can provide protection against SHIV and help determine the concentration of antibodies that a vaccine would need to generate to be protective, they said.
They concluded that an effective HIV vaccine targeting the HIV fusion peptide likely will need to expand upon the concepts used in this study, by generating multiple varieties of fusion peptide–directed antibodies. This would increase the likelihood that the vaccine could maintain a preventive effect across the vastly diverse HIV variants in circulation.
