Artist's rendering of an HIV virus.
Credit: iStockphoto
SCOTLAND: In 2007 a major HIV vaccine trial ground to a halt when the results showed that it actually increased rates of infection. Now researchers may have discovered why.
The team, led by Steven Patterson of Imperial College in London and the U.K. HIV Vaccines Consortium, have published a study in PNAS this week. It shows that before the vaccine had a chance to protect people, it may have prompted CD4 cells - the very cells that are vulnerable to HIV - to be in just the right place to encounter the virus.
Not so harmless vectors
HIV vaccines use harmless viruses called vectors to present parts of HIV to the immune system. This primes the immune system to recognise and destroy the real virus when infection occurs at a later date.
The vector used in the 2007 'STEP' trial was adenovirus 5, and intriguingly those vaccine recipients that had previously come into contact with this virus were the ones that were more likely to become infected with HIV.
Patterson said that, in his tests, CD4 cells from healthy volunteers, who had been previously infected with adenovirus 5, recognised the vaccine vector and then behaved as though they were trying to fight a new adenovirus 5 infection. The problem is that adenovirus 5 often causes gut infections, so the cells in Patterson's experiment started to make homing molecules that guide the CD4 cells to the gut surface.
For the mainly homosexual male participants of the STEP trial, an increased number of CD4 cells in their intestines - the entry portal for the virus - could have put them at increased risk of HIV infection.
Controversial findings
Patterson cautioned that at this stage his results are controversial. "But we would propose that the results of our study offer an explanation for the increased rate of infection [in the STEP trial]," he said.
Pat Fast, chief medical officer of the International Aids Vaccine Initiative in New York City, USA, describes the research as "important", but adds that we don't know how these results will translate to heterosexual HIV transmission and to injection drug populations. She says "one of the next steps is to see how this research relates to heterosexual sex in the real world."
Similar problems could dog other HIV vaccines that use common human viruses as vectors. "If we are right", said Patterson, "any virus vector that naturally enters through the mucosal [internal body surface] route may cause similar problems."
But, although the results may leave HIV vaccine research looking ever more complicated, "it will lead scientists to better define how vaccines will affect different components of the immune response," said Fast. In doing so, it can only bring scientists closer to developing a reliable and safe vaccine.
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