An HIV vaccine that famously increased its recipients' vulnerability to HIV infection could have done so by unintentionally stimulating the immune system, say scientists.
In 2007 the Step HIV vaccine trial was halted when results showed that people who received the vaccine were more likely to get HIV than those receiving no vaccine.
The risk was greater in people previously infected with a common virus called adenovirus 5 and in uncircumcised men.
Now a team of scientists led by Steven Patterson of the UK HIV Vaccines Consortium may have discovered why previous infection with adenovirus 5 increased the risk of HIV infection. The research is published in Proceedings of the National Academy of Sciences (PNAS) this week (16 November).
HIV vaccines use inactive viruses to introduce parts of HIV into the body to cause an immune response that should prevent future infection. The Step trial used inactive adenovirus 5 for this purpose.
Patterson thinks that the immune systems of people previously infected with adenovirus 5 recognised the virus, causing immune cells called CD4 cells — which are vulnerable to HIV — to move to parts of the body where they would fight adenovirus 5.
However, in these areas, such as the vagina, CD4 cells are more likely to encounter HIV and to become infected.
"Our research suggests that the adenovirus-based HIV vaccine effectively instructs [CD4 cells] to gather around exactly where HIV is likely to be introduced," said Patterson.
The theory is based on laboratory tests showing that CD4 cells from people previously exposed to adenovirus 5 were activated by adenoviruses.
"Their evidence is intriguing," said Pat Fast of the International Aids Vaccine Initiative. "However, at this stage it remains controversial."
"Patterson's research assumes that prior exposure to adenovirus 5 was the key factor leading to increased HIV infection," she added, but scientists do not yet know the importance of the lack of circumcision.
Patterson said that a similar effect could be seen with other vectors that infect us through the same body surfaces as HIV.
But other viruses use different routes and "it does not follow that other vaccine vectors will do the same as adenovirus 5", says Ian Jones, professor of virology at Reading University, United Kingdom.
Nevertheless, Fast says that Patterson's research "will lead scientists to try to look more critically at the immune responses to vaccines in their early stages of development".
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PNAS doi 10.1073/pnas.0907898106c (2009)