Natural immunity

We know an HIV vaccine must be possible. For example, on average ten years elapse from the time one is infected with HIV to the time when the virus has done enough damage to warrant an AIDS diagnosis. This means that the immune system has some ability to control HIV, albeit temporarily. During this time a viral load which, in acute infection, peaks at several million copies per ml is typically contained to some tens of thousands of copies. The role of a vaccine could be to improve these defences to a point at which they would contain HIV replication more completely, and permanently.

Additionally, there are individuals who exhibit an exceptional ability to shrug off HIV infection, and analysing what is different about their immune systems yields ideas for vaccines. For example, some female sex workers and partners of gay men have remained HIV uninfected, or infected but able to control infection so it is harmless, for many years, despite repeated sex without condoms.

About 2% of people with HIV (the precise proportion depending on definition) are ‘long-term non-progressors’ who maintain high CD4 counts and still do not need medication after more than 20 years of infection.

A smaller proportion are so-called ‘elite controllers’ who in addition maintain undetectable or consistently low viral loads.

So some people have immune responses that seem to be able to control HIV replication just as well as an antiretroviral regime. However, on the other hand, the natural hosts of simian immunodeficiency virus (SIV) such as the sooty mangabey maintain high viral loads without seeming to suffer any immune damage. Researchers are building and testing vaccines designed to stimulate the immune cells that are believed to be responsible for the apparent acquired immunity either to the virus or to its effect on the immune system.

Already experimental vaccines against SIV, a close cousin of HIV that infects monkeys, have been shown to prevent AIDS (Shiver 2002). However, what works in animals does not always translate into success in humans; results from these experiments led to only the second large human trial of a candidate vaccine, the STEP trial of the Merck trivalent adenovirus-5 vaccine, which started in May 2006. However, in what may have been the biggest setback so far in HIV vaccine development, the STEP trial was closed in September 2007 when it was found that the vaccine was, at the very least, ineffective (Robertson 2008).

Before we look at the importance of the STEP trial result, however, we need to look at exactly how an HIV vaccine might work, and which strategies have been tried so far.