Antibodies protect against HIV in animal studies

Human antibodies

Three different HIV antibodies each 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 people.

The antibodies – a human broadly neutralsing 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.

According to the authors, 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 study, published in Science Translational Medicine, was led by the Vaccine Research Center (VRC) at the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health.

The SHIV study in rhesus macaques

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 who previously 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 intravenous infusion of one type of antibody – a 2.5 or 10mg/kg of bodyweight dose of VRC34.01, or one of the two vaccine-elicited rhesus macaque antibodies – 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 strain of SHIV known to be sensitive to fusion peptide-directed antibodies.

All monkeys that received a placebo infusion acquired SHIV following the challenge. Among monkeys that received VRC34.01 infusions, none receiving the 10mg/kg dose and 25% of those receiving the 2.5mg/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.

The three antibodies studied each provided statistically significant protection from SHIV, and the effect was dose dependent, that is, highest in monkeys with greater antibody concentrations in their blood.

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