Coverage of CROI 2008 (Conference on Retroviruses and Opportunistic Infections)

February 4–6, 2008, Boston, MA

 

Assessment of HIV vaccine research discouraging

by Martin Delaney, February 5, 2008

Noted HIV vaccine researcher Ron Desrosier of the New England Primate Center at Harvard Medical School delivered a sobering assessment of the state of vaccine research on the second day of CROI. While nothing presented was new, the conclusions he drew were perhaps the most discouraging assessment yet of the recent failure of the Merck/NIAID T cell vaccine.

His presentation is likely to have a powerful impact in coming months as researchers and funders decide whether to proceed with more studies of this type of vaccine. Before the failure of this vaccine was announced, plans were underway to launch a larger study of slightly different version of a T cell vaccine. Now, those plans are at best uncertain.

Desrosier began by asking the question: “Is an effective HIV vaccine feasible?” Before answering, he listed several reasons why making an HIV vaccine is such a difficult scientific challenge.

1. The natural immune response against HIV fails to rid the body of the disease. At the heart of the concept of vaccines is that they’re supposed to trigger, in advance, the normal immune reaction the body makes against an infection. With HIV, there is no successful immune reaction, at least not one sufficient to rid the virus.
2. The natural immune response against HIV does not fully protect against superinfection, or a second infection with HIV. There are now many documented cases of superinfection.
3. HIV “spits out” escape variants. In other words, it constantly makes mutated HIV which isn’t controlled by the immune response against the original virus that started the infection.
4. HIV makes products that help it evade immune response.
5. HIV destroys the very helper cell activity that would normally help the body rid itself of the virus.
6. Finally, HIV creates an incredible number of variations. To explain how big a factor this is, Desrosier pointed out that HIV produces more variations in a single person than the influenza virus creates worldwide.

After discussing this list, he returned to the question: Is an HIV vaccine currently feasible? The answer, he proclaimed, is “No”.
Next he asked whether we should be surprised that the Merck/NIAID vaccine failed. He reviewed some history of the vaccine and responses seen in animal studies and concluded that the answer again was “No”. He argued that there was no reason to expect it to work.

Next he asked whether any of the current vaccine candidates had a chance to show efficacy. He quickly answered “No”. He extended the question by asking whether there was anything to be learned by testing these vaccines in people, and the answer he gave again was “No”. The implication of his answers to these questions was that no further clinical vaccine studies should be run until there’s a reason to believe that they will work. This was critical because it was his way of saying that the next large planned vaccine study, called PATH, scheduled to begin this year, should be stopped.

Fortunately, he also had some ideas how to proceed. His solution is redirect vaccine spending to a new round of discovery or basic research on how to elicit potent neutralizing antibodies, what constitutes a true protective response, and how to develop novel vaccine and prevention efforts. These suggestions, however, were sadly short on detail. Few would dispute that these questions are important, but people have been asking them for decades with little success.

Not everyone shares Desrosier’s bleak assessment. We spoke with the Director of NIAID, Anthony Fauci, representatives from Merck, and other vaccine researchers. While all agreed that new strategies were needed, they didn’t agree with some of Desrosier’s claims. For example, some felt he was misleading when he suggested that there were no data to support the Merck/NIAID vaccine. Instead, they say that the animal data were the best and most comprehensive yet seen for an HIV vaccine and that Desrosier himself had encouraged Merck to partner with NIAID to conduct human studies. Others argued that it was unfair to suggest that NIAID was to blame or had “lost its way on HIV vaccine research” as Desrosier asserted. They claimed that NIAID can only fund the proposals that scientists submit. It doesn’t write the proposals or design the studies.

The one sure conclusion from the events of recent months is that current vaccine designs seem to have hit a dead end. New approaches are clearly needed. It will likely be more effective for people to pull together than to blame each other for the past failures.