New insights into how a promising HIV vaccine works are provided in a study published by Cell Press January 10th in the journal Immunity. By analyzing the structure of antibody-virus complexes produced in vaccine recipients, the researchers have revealed how the vaccine triggers immune responses that could fight HIV-1 infection. The study could help guide efforts to increase the vaccine's production, which currently is not high enough for clinical use.
"This is the first comprehensive study of the repertoire of antibodies that were induced by an HIV vaccine and were associated with decreased transmission of HIV," says senior study author Barton Haynes of Duke University Medical Center. "Ultimately, the motivation of the study is to understand how that vaccine works in order to develop ways to make it better."
An estimated 34 million people around the world live with HIV, and the development of a safe and effective vaccine is a global priority. In 2009, a vaccine efficacy trial revealed that the RV144 HIV-1 vaccine protected nearly a third of recipients from infection. In a more recent study, Haynes and his collaborators found that vaccine-induced antibodies targeting variable regions 1 and 2 (V1-V2) of the virus are associated with a decreased risk of HIV-1 infection. But until now it has been unclear whether these antibodies are crucial for protection against the virus or how they might fight off infection.
To address these questions, Haynes and his team isolated antibodies from RV144 vaccine recipients and determined the antibodies' crystal structures both alone and in complex with HIV-1. They found that the V2 region, which is targeted by the antibodies and includes amino acid residue 169, exhibits extreme variation in both its amino acid sequence and its structural conformation. Despite this variation in HIV-1, the antibodies can recognize position 169 on the virus and thereby bind to virus-infected immune cells and mark them for destruction.
The discovery of variation in the sequence and structure of HIV-1's V2 region opens up new avenues for designing vaccines capable of providing more protection than the existing RV144 vaccine. "New technology is allowing the dissection of a complex set of vaccine-induced responses such that new vaccines can be designed to hopefully improve on the beachhead that the RV144 trial provided to the HIV-1 vaccine field," Haynes says.
Immunity, Liao et al.: "Vaccine Induction of Antibodies Against a Structurally Heterogeneous Site of Immune Pressure within HIV-1 Envelope Protein Variable Regions 1 and 2."