HIV antibodies protect animals in proof-of-concept study

Three different HIV antibodies each independently protected monkeys against acquisition of simian HIV (SHIV) in a placebo-controlled proof-of-concept study intended to inform the development of a preventative HIV vaccine for humans. The antibodies – a broadly neutralizing human 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.

The study, published in Scientific translational medicinewas led by the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

Antibodies that target the fusion peptide can neutralize various strains of HIV in vitro, that is, in a test tube or culture dish outside of a living organism. The NIAID VRC isolated a human antibody against a fusion peptide, 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 an immune system similar to humans, that had previously received a vaccine regimen designed to generate antibodies against fusion peptides.

Demonstrating that these antibodies protect animals would allow the fusion peptide to be validated as a target for the design of human vaccines. SHIV challenge – the administration of an infectious dose of SHIV – to rhesus macaques is a widely used animal model to evaluate the performance of HIV antibodies and vaccines.

In this study, rhesus macaques in each of four groups received a single intravenous infusion of one type of antibody (a dose of 2.5 or 10 mg/kg body weight of VRC34.01, or one of two rhesus macaque antibodies elicited by the vaccine) and other monkeys received a placebo infusion. To determine the protective effect of the antibodies, each monkey was challenged five days after infusion with a SHIV strain known to be sensitive to antibodies against the fusion peptides.

All monkeys infused with placebo acquired SHIV after challenge. Of the monkeys receiving VRC34.01 infusions, none received the 10 mg/kg dose and 25% of those receiving the 2.5 mg/kg dose acquired SHIV. Among those who received the vaccine-induced 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 acquired the SHIV.

Over time, the concentration of antibodies in the blood of animals given DFPH-a.15 decreased. These animals were re-challenged 30 days later to see if the lower concentration of antibodies had a diminished protective effect, and half of them acquired SHIV.

The three antibodies studied each provided statistically significant protection against SHIV, and the effect was dose dependent, that is, it was greatest in monkeys with higher antibody concentrations in the blood.

According to the authors, these results represent proof of concept that antibodies against fusion peptides can provide protection against SHIV and help determine the concentration of antibodies a vaccine should generate to be protective. They suggest that their findings about vaccine-elicited antibodies in some animals support continued work to design preventative HIV vaccine concepts targeting the fusion peptide.

The authors conclude that an effective HIV vaccine targeting the HIV fusion peptide will likely need to expand on the concepts used in this study, generating multiple varieties of antibodies against the fusion peptide. This would increase the likelihood that the vaccine could maintain a preventive effect against the very diverse HIV variants in circulation.