Quest for the AIDS vaccine

doi:10.1136/bmj.39240.416968.AD

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Alison Tonks, associate editor

BMJ, London WC1H 9JR

atonks{at}bmj.com

Researchers broadly agree that the best way to halt the AIDS epidemic is to develop a vaccine against HIV. But despite huge investment a vaccine is proving elusive, as Alison Tonks explains

The AIDS pandemic is now more than 25 years old, and for most of its history, scientists have been searching for an effective vaccine against HIV. There have been many false dawns, dashed hopes, and disappointments along the way as evangelical rhetoric has eventually given way to a more pragmatic acceptance that a vaccine would be great, and may even be possible, but it won't be on offer at a clinic near you any time soon. The most optimistic experts predict it will be at least another 10 years before any kind of vaccine is available1; the most pessimistic say it could take 50. Even then, the first vaccines will probably be only partially effective.2 Why is such an important task taking so long?

The trouble with HIV

HIV is one of the most complex viruses ever identified, and it's extremely good at evading any immune mediated strategy directed against it. HIV is already genetically diverse—there are currently nine genetic subtypes (or clades) of HIV1, the most prevalent strain—and new forms are emerging all the time. HIV mutates rapidly so scientists are trying to hit a constantly moving target.3 4 Any successful vaccine must be effective against multiple subtypes and will need constant surveillance and modification to keep it ahead of the inevitable steady stream of new variants.

HIV has a full menu of other defences. Critical surface proteins that help HIV enter human cells are protected by a layer of sugary molecules called N-linked glycans and by the ability to change shape during the process of infection. It's also a retrovirus, inserting its own genetic material …