Q and A with Barton Haynes
While the use of antiretroviral therapies to prevent HIV infection will likely dominate the scientific agenda at the 19th International AIDS Conference (AIDS 2012) in Washington, D.C, July 22-27, researchers are also paying attention to AIDS vaccines. VAX Science Writer Regina McEnery recently caught up with Barton Haynes, a Duke University professor who leads the virtual consortium known as the Center for HIV/AIDS Vaccine Immunology (CHAVI), to hear more about new findings from the RV144 trial in Thailand and the search for more potent and broadly neutralizing antibodies against HIV, which will be the subject of his July 25 plenary talk at AIDS 2012.
Even the most optimistic people feel an AIDS vaccine with sufficient efficacy is still years away. Will we get there?
I’m hoping that we will and I’m optimistic that we will.
What will be the main highlights of your talk?
The new findings that have energized the AIDS vaccine field. These findings will include identifying the immune correlates of infection risk in the RV144 trial, the elucidation of many transmitted/founder viruses (the viruses that cause infection in human to human transmission), the discovery of broadly neutralizing antibodies (bNAbs), and insights as to why bNAbs have been so difficult to induce. Everyone believes these new discoveries can provide important clues to speeding up the development of a preventive vaccine. Seven to eight years ago, the field was frustrated that we didn’t know what to do and we certainly didn’t know how to do it. What is different now is we have clues. We do know some people can make [potent] antibodies over long periods of time that we want to elicit over a shorter period of time in a vaccine.
Is the vaccine problem solvable?
The observation that there appear to be antibodies that can hit the Achilles heel of the Envelope [HIV’s surface protein] and be made in certain people is one indication that this is a solvable problem. The immune correlates of infection risk found in the RV144 trial are also clues for further studies. I think there are strategies based upon these observations that the field is beginning to explore.
Can you describe one of those strategies?
Most of the bNAbs are unusual in some respects. These unusual characteristics are in general indications that they are the products of either quite convoluted or disfavored developmental pathways. There are a series of technologies that have been developed whereby these pathways can be determined and studied with the goal of trying to recreate the pathways with a series of vaccine immunogens [active ingredients in vaccines] that can bypass these torturous pathways and follow more productive pathways.
As antibody clones expand, they undergo changes. An antibody that travels down a short developmental pathway has fewer changes, whereas those traveling down longer pathways have more changes. Many of these bNAbs are among the [most] mutated and changed antibodies. Most of the vaccine [candidates] we have now induce antibodies that only have a few changes in their building blocks, whereas it takes several years of continuous stimulation of the immune system by the infecting virus to drive these mutations or changes in the bNAbs. We want to drive antibodies to have more mutations but to use a shorter pathway and we are just now exploring ways to do that.
This sounds complicated.
HIV is different from other viruses for which successful vaccines have been made because, among these, HIV is the only virus that has the trait of integrating into the host genome. Unlike any other vaccine, we will have to have sterilizing immunity at the time of HIV transmission for a vaccine to be successful.
When will we be able to test a candidate derived from these strategies?
We are in preclinical studies in non-human primates now. The timing of human studies will depend on the outcome of these preclinical studies.