• There are major scientific obstacles to creating and testing a preventive HIV vaccine either to protect against HIV infection or to modify the course of the disease. Nonetheless, if these can be overcome, even a partially effective vaccine would be of great public health benefit. The research is also likely to yield valuable insights into immune responses to HIV.

• A variety of approaches to vaccine development have been explored for HIV. Most of these have not previously been used to make licensed vaccines against other viruses.

• Traditional approaches - using a weakened strain of the virus (a 'live attenuated vaccine') or an extract of a cell culture (a 'killed virus') - are considered too dangerous for HIV, but safer equivalents are being pursued.

• A therapeutic vaccine is a vaccine which is given to people already infected with HIV. It is hoped that the immune system's reaction to the vaccine will prevent the progression of HIV disease, although proving this may not be easy.

• 'Recombinant subunit' vaccines, based on a protein from HIV's outer envelope called gp120 were the subject of the first full-scale HIV vaccine efficacy trials to be completed. These trials found no difference in rates of HIV amongst people who received the vaccine, compared to those who did not, so it is clear that this relatively simple approach to a vaccine does not work.

• The most promising approaches appear to be based on more complex vaccine systems.

• One strategy is to present multiple HIV proteins in ways that stimulate immune responses against HIV-infected cells, selecting so-called 'killer T-cells'. One way to achieve this may be to present HIV gene sequences repeatedly, in a 'prime/boost' arrangement, so that HIV proteins are made inside human cells. It may be possible and necessary to ensure that genes are expressed for an extended period, by using specially chosen vector systems. Clinical trials have either begun or are in the planning stages for several vaccines and vaccine combinations of this kind.

• Another strategy is based on modifying HIV's envelope proteins or mimicking small regions of the virus's surface, with a view to creating stronger and more effective antibody responses than occur naturally.

• There is a lot of research still to be done, to establish the kind of immune response that is really needed and how best to induce it.

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