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New Target for HIV Vaccines

watkins
Image: University of Wisconsin/Jeff Miller

HIV is a tricky virus that can beat treatment by changing its nature. Indeed, patients taking AZT and other AIDS drugs often wind up harboring variant, drug-resistant strains of HIV as a result. But in today's issue of Nature, researchers report that early immune attacks on the virus, mediated by killer T cells, can also bring about substantial selective pressure. And because the rates of selection in both cases are similar, the scientists suspect that these early immune responses--if they can be honed by way of a vaccine--might prove as effective as certain drug treatments in controlling HIV.

David Watkins (right) and his colleagues at the University of Wisconsin at Madison studied rhesus macaques infected with the simian version of HIV, tracking changes in the viral strains and in the animals' immune responses. They found that shortly after infection, the immune system sicced killer T cells on the original strain, but that before that response was fully developed, the virus changed. After four weeks the predominant viral particles bore so-called Tat proteins no longer recognized by the host's immune system.

"This is an example of Darwinian selection for viruses that evade immune responses and has many implications for novel vaccine approaches," Watkins says. "If vaccines can induce these killer T cell responses before infection occurs, the opportunity for the virus to subsequently escape from these immune responses would be greatly reduced." Until now, such early responses have been overlooked because they are typically long gone in humans by the time the infection can be detected. Watkins and his team, however, have begun vaccinating monkeys with regions of the Tat protein that they have shown to be recognized by the killer T cells.

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