Difficulties associated with vaccine development

A number of attributes of HIV and its mode of infection conspire to render development of an effective vaccine less than straightforward. These factors include:

• HIV displays extensive genetic variation even within a single individual. Such genetic variation is particularly prominent in the viral env gene whose product, gp 160, is subsequently proteo-lytically processed to yield gp 120 and gp 41.

• HIV infects and destroys T-helper lymphocytes, i.e. it directly attacks an essential component of the immune system itself.

• Although infected individuals display a wide range of antiviral immunological responses, these ultimately fail to destroy the virus. A greater understanding of what elements of immunity are most effective in combating HIV infection is required.

• After initial virulence subsides, large numbers of cells harbour unexpressed proviral DNA. The immune system has no way of identifying such cells. An effective vaccine must thus induce the immune system to (a) bring the viral infection under control before cellular infection occurs or (b) destroy cells once they begin to produce viral particles and destroy the viral particles released.

• The infection may often be spread not via transmission of free viral particles, but via direct transmission of infected cells harbouring the proviral DNA.

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