Progress in the development of an HIV vaccine

Despite the remarkable advances that have been made in the last 20 years regarding the molecular virology, pathogenesis and epidemiology of HIV, the development of an effective HIV vaccine remains an elusive goal. The major reason for this is that we have not determined a correlate of immunity. The various explantations for this include integration of the virus into the host cell genome, infection of long-lived immune cells, HIV genetic diversity (especially in its envelope), persistent high viral replication releasing up to 10 billion viral particles per day and/or production of immunosuppressive products or proteins. However, there is evidence that the host can be protected: some highly exposed persons have remained uninfected; the relatively low incidence of mother to child (fetus) transmission; the initial effective immune response that significantly, if temporally, reduces viral loads; some infected persons are long-term non-progressors; experimental vaccines and passive immunisation have proven effective in experimental animals; and finally, successful vaccine development against other viral infections. At this time, the experimental vaccine pipeline is quite robust and ranges from HIV proteins (although the first such vaccine, recombinant gp120 made on Chinese hamster ovary cells, failed to protect volunteer men having sex with men [MSM]) to DNA vaccines and various novel delivery strategies. Perhaps the greatest impediment is the requirement to test these experimental vaccines in resource-poor developing countries that, at present, lack the necessary infrastructure for performing large, long-term, scientifically valid studies.