A Promising, “Unusual” Approach to Targeting HIV Spike Protein

Research Question

The extraordinary feats of global eradication of smallpox and near-eradication of polio would not have been possible through treatment alone. Anti-virus vaccines proved to be the decisive factor in both cases—they are also the primary mechanism by which the world seeks to suppress COVID-19.

The realization—that treatment alone is not enough to stop most viral epidemics—has made repeated failures over the past four decades to develop an effective HIV vaccine all the more disappointing. Most recently, a trial in South Africa of an HIV vaccine based on the same technology used in the successful Johnson & Johnson COVID-19 vaccine failed to provoke an immune response sufficient to block HIV infection.

New ideas are required, both in terms of what to present to the immune system and the type of platform delivering that information. For example, Moderna recently announced that it would test an HIV vaccine based on its mRNA coronavirus vaccine technology, but there is no firm basis to anticipate that this strategy will be effective.

Findings

The ability of HIV to infect a cell is dependent on its envelope sugar-protein spike, which consists of three external gp120 proteins and three gp41 proteins that extend into the membrane of the virus. This structure must undergo extensive changes in shape upon interacting with the host cell through CD4.

In this study led by amfAR Krim Fellow Dr. Marit van Gils, a series of monoclonal antibodies were generated from rabbits immunized with a chemically stabilized form of the gp120/gp41 trimer. Each resulting antibody was then tested for its ability to neutralize different isolates of HIV.

The research team identified a new dominant area on gp41 and found that antibodies recognizing this area approached the envelope spike from “unusual angles.” This “unusual” approach translated into better virus neutralization.

Impact

The authors conclude that their strategy “can be used to shape the next generation of HIV-1 immunogens to elicit improved responses after vaccination.”

amfAR’s Role

amfAR was a funder of this research.  

Original Article

http://www.ncbi.nlm.nih.gov/pubmed/34076487

Dr. Laurence is amfAR’s senior scientific consultant

---