Towards an improved HIV Vaccine

13 January 2013
Posted by Ben Valsler.

New insights into the mechanism behind a promising HIV vaccine could point drug development in the right direction for a more effective, and much needed, vaccine, according to research published in the journal Immunity.

In 2009, a trial in Thailand of a potential HIV vaccine showed around 30% effectiveness in at-risk populations.  Although this is very promising, it is thought that a vaccine would need to be at least 50% effective in order to slow the spread of the disease.  Now, researchers including Duke University's Barton F. Haynes have explored the antibodies induced by the vaccine to find out how it targets the virus.

HIV-1 particles assembling at the surface of an infected macrophage.In the original vaccine trial, 89% of breakthrough infections were with a particular family of virus strains.  Genetic analysis then suggested to the authors that the vaccine had increased efficacy against viruses with a particular amino acid present in a highly variable region called V2.  When they then isolated the antibodies and determined their structure both alone and when attached to HIV, they confirmed affinity for the V2 region.

Variable regions, by their very nature, may not seem a particularly attractive vaccine target.  Much of the vaccine development effort has gone into targeting well-conserved regions, but these are actively hidden from the immune system.  The authors argue that:

"For RNA viruses such as influenza and HIV-1, which are highly divergent and capable of rapid genetic alteration is the divergent regions that may be more susceptible to antibody-mediated neutralization."

And add that: "Despite extraordinary variation in both sequence and structure, the humoral immune system appears capable of recognizing V1-V2 in the setting of vaccination ... and immunogens that focus the elicited response to this V2 region should be explored."

This gives vaccine designers a new set of potential targets and sheds light on the tools our immune system provides in the battle against HIV.

Add a comment