Why is HIV so difficult to vaccinate against?

• HIV, however, has no sufficiently close harmless relative. And it's brilliant at overcoming the immune system's defences (as it does with Aids).
• The first and most obvious strategy is to inject the patient with an HIV virus that has been weakened - 'attenuated' - so that it can't cause a runaway infection. Unfortunately, even attenuated HIV gave young monkeys Aids when it was tried, so that strategy is out.
• So vaccines have to use inactive components of HIV, either by themselves or wrapped up inside the shells of other viruses, to create a 'fake' infection

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Antibody vaccines

• The next most obvious strategy is just to use the surface shell of HIV - its 'envelope' protein, the main bit of which is called gp120. This is the basis of the VaxGen vaccine - the first-ever to undergo a large-scale 'phase III' human trial on 8,000 patients, with results due in the first quarter of 2003. This induces a strong antibody response (see below). But it's nonetheless not expected to protect against most HIV infections.
• This is because the envelope protein of HIV is hyper-variable. The parts that induce the immune response are not essential to making the virus work, so HIV can afford to let them change - 'mutate' - all the time. The virus you catch may have an unrecognisably different envelope to the one you got in a vaccine.

A trip into the immune system

• Head spinning yet? Before we go any further, we have to take a side trip into the workings of the immune system.