The researchers found that three different HIV antibodies directed against the fusion peptide protected monkeys from simian HIV infection, providing good implications for HIV vaccine development.Three different HIV antibodies each independently protected monkeys from simian HIV infection (SHIV) in a placebo-controlled proof-of-concept study designed to inform the development of a preventive vaccine against HIV in humans.

Transmission electron micrograph of HIV-1 virion (red) germination and replication from a segment of chronically infected H9 cells (blue). Granules are in different stages of maturation; arcs/semi-circles are immature granules that are starting to form, but are still part of the cell. The morphology of immature particles will slowly transform into mature forms, showing the typical "conical or spherical core". Image taken at the NIAID Integrated Research Facility (IRF) at Fort Detrick, Maryland. Image source: NIAID

The antibodies - one human broadly neutralizing antibody and two isolated from previously vaccinated monkeys - target the fusion peptide, a site on HIV's surface protein that helps the virus fuse with and enter cells.

The study, published in Science Translational Medicine, was led by the Vaccine Research Center (VRC) of the National Institute of Allergy and Infectious Diseases (NIAID), a subsidiary of the National Institutes of Health.

Antibodies targeting the fusion peptide can neutralize a variety of HIV strains in vitro (that is, outside the living body in a test tube or dish). The NIAIDVRC isolated a fusion peptide-directed human antibody, named VRC34.01, from an HIV-infected person who donated blood samples for research. They also isolated two antibodies from macaques - whose immune systems are similar to those of humans - that had been treated with a vaccine designed to produce fusion peptide-directed antibodies.

Demonstrating that these antibodies protect animals would validate the fusion peptide as a target for human vaccine design. SHIV challenge—injecting macaques with an infectious dose of SHIV—is a widely used animal model to evaluate the performance of HIV antibodies and vaccines.

Experimental results and implications

In the study, four groups of macaques each received a single intravenous infusion of an antibody - VRC34.01 at doses of 2.5 or 10 mg/kg body weight, or one of two vaccine-induced macaque antibodies - while the other monkeys received a placebo infusion. To determine the protective effect of the antibodies, each monkey was challenged five days after the infusion with a strain of SHIV known to be sensitive to fusion peptide-directed antibodies.

All of the placebo-infused monkeys became infected with SHIV after being challenged. Among the monkeys that received VRC34.01 infusions, none of the monkeys who received the 10 mg/kg dose were infected with SHIV, and 25% of the monkeys who received the 2.5 mg/kg dose were infected with SHIV. Among monkeys that received vaccine-induced antibodies from macaques, none of the monkeys that received the antibody, called DFPH-a.15, became infected with SHIV, while 25 percent of the monkeys that received the antibody, called DF1W-a.01, became infected with SHIV. Over time, the antibody concentrations in the blood of animals that received DFPH-a.15 antibodies decreased. The animals were challenged again 30 days later to see if lower concentrations of antibodies reduced protection, and half of the animals became infected with SHIV.

All three antibodies studied were statistically protective against SHIV, and this effect was dose-related, meaning monkeys with higher concentrations of antibodies in their blood had stronger protection.

Research findings could help develop effective HIV vaccine

The authors say these findings demonstrate that fusion peptide-guided antibodies can provide protection against SHIV and help determine what concentration of antibodies a vaccine needs to produce to be protective. They believe the vaccine-induced antibodies they found in some animals support further efforts to design preventive HIV vaccine concepts that target fusion peptides.

The researchers concluded that an effective HIV vaccine targeting HIV fusion peptides will likely require extending the concepts used in this study to generate multiple fusion peptide-directed antibodies. This would make it more likely that the vaccine would remain protective across the multiple HIV variants in circulation.

Compiled source: ScitechDaily