A Much Anticipated HIV/AIDS Vaccine Trial Fails

The buzzword describing the failure of the recent much-lauded STEP HIV-1 vaccine clinical trial is "disappointing". I would add "but not surprising". Unfortunately, when we really think about the fundamental unknowns in the host-pathogen relationship between HIV and humans, perhaps there is little reason to expect that our current understanding of how HIV interacts with the human immune system would lend itself to engineering an efficacious vaccine. After all, what are the true correlates of immunity against HIV? Which of the many branches of the immune response is capable in humans of actually preventing infection by a challenging HIV virus? How is such an immune response triggered? Perhaps lentiviruses, or retroviruses in general, are capable of immune evasion on a vast, evolutionary scale .. which might be why our genomes are littered with silenced retroviral sequences, why primates have evolved specific anti-retroviral defenses intrinsic to the cell (like APOBEC proteins and TSG101), and why HIV long-term non-progressors tend to block HIV at the entry step. HIV might even mimic HERV to some extent, and be seen as 'self' by the immune system.So what can we do today? I think that unfortunately, we have to move into a realm of phase I clinical trials that tests specific hypotheses about mounting an effective immune response to HIV with a robust outcome of "Yes" or "No" rather than with the aim of pushing a marginal vaccine candidate into larger phase II and III trials without really understanding the basis for efficacy in pre-clinical and phase I trials. This is the way good science can be done. It's not satisfying if one has the disease today, but perhaps we have no choice.In the meantime, a vastly expanded effort to distribute anti-retroviral drugs and prevention, with a real "Marshall Plan" for building health care delivery systems in the worst-hit regions of the world, is the stop-gap solution.For more about the HIV vaccinology, see the AIDS Vaccine Advocacy Coalition. It was World AIDS Day on 1 December: President Bush has called for another $30 billion for AIDS relief, and that is a good thing.