The failure of the recent HIV STEP trial represented a serious blow to the development of an AIDS vaccine. Two papers published in Nature Medicine rule out a leading explanation for this failure.
In the STEP trial, participants were vaccinated with a weakened form of a common cold virus (Ad5) which was altered to carry three HIV genes. It was believed that stimulating the immune system with these weakened HIV genes would lead to a more aggressive response to HIV if and when the participant was exposed to it. However, the vaccine resulted in increased HIV-1 acquisition, particularly if the volunteer had high levels of Ad5-neutralizing antibodies, which are often observed.
Since HIV-1 targets the body's T cells, the STEP trial results led to the hypothesis that vaccination of individuals with high levels of Ad5 antibodies had an increase in their T cell numbers, which served as targets for the HIV-1 infection.
The two groups lead by Dan Barouch and Michael Betts found that there is no correlation between baseline levels of Ad5-specific neutralizing antibodies and Ad5-specific T cell responses. Moreover, individuals with high levels of Ad5 antibodies do not develop higher Ad5-specific immune responses after vaccination compared to individuals with low levels of Ad5 antibodies.
Although these findings indicate no direct role for the Ad5-specific T cells in increasing HIV-1 susceptibility in the STEP trial, the true reason for its failure remain a mystery.
Dan Barouch (Beth Israel Deaconess Medical Center, Boston, MA, USA)
Michael Betts (University of Pennsylvania, Philadelphia, PA, USA)
Abstracts available online:
Abstract of Paper 1.
Abstract of Paper 2.
(C) Nature Medicine press release.
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