Comprehensive Mapping Provides Insight into HIV Antibody-Escaping Mutants

The key part in developing HIV vaccines and antibody immunotherapeutics is by defining how viral mutations affect the sensitivity of HIV to broadly neutralizing antibodies.

In a study published in Cell Host & Microbe, investigators successfully mapped all mutations that help HIV evolve away from the PGT151. The mutations discovered are a mixture of those that were previously discovered and some newly discovered sites.

The investigators used a library of HIV envelopes (Env) to infect T cells in the lab in the presence of PGT151, a broadly neutralizing antibody that recognizes a combination of Env residues and glucans. Env mutates can rapidly hide from immune recognition before the body can successfully rid itself of the infection.

To determine which mutations allowed HIV to escape PGT151, the investigators sequenced the mutant viral strains that could infect cells in the petri dish in the presence of the antibody.

The authors noted the importance of this step, because it allows them to gain a better understanding of the evolutionary paths HIV could use to escape a broadly neutralizing antibody, and ultimately understand how to block the paths through better vaccines.

“If we can understand where the antibodies bind, we can engineer vaccines that elicit more of those types of antibodies,” said investigator Dr Jesse Bloom. “And when we find really good antibodies, we can understand what parts of the virus are sites of vulnerability.”

Indirectly, the study also provides an inferred map of where a given antibody binds to a given virus—–a method that is simpler than 3D crystallography.

Although there are many working vaccines available against other viruses that scientists do not fully understand, with HIV, more rationale on how to make vaccines for HIV will be required.

“Comprehensively mapping HIV antibody escape gives a quantitative, mutation-level view of Env evasion of neutralization,” the authors concluded.