Abstract

As the HIV-1 epidemic continues to spread world wide, the need for an effective vaccine remains urgent. Efforts to develop such a vaccine have been hampered by three main factors: (a) the extraordinary ability of the virus to mutate; (b) inability of most known specificities of anti-HIV antibodies to neutralise HIV primary isolates consistently; and (c) lack of understanding of the correlates of protective immunity to HIV infection. In view of the complex biology of HIV-host interactions, the most fruitful avenue may be development of multivalent HIV immunogens tailored to HIV isolates in specific geographical locations.

PIP:

HIV has a tremendous ability to mutate. Most known specificities of anti-HIV antibodies cannot neutralize HIV primary isolates consistently. Scientists do not understand the correlates of protective immunity to HIV infection. These three factors have thwarted efforts to develop an effective HIV vaccine. The fact that there is a large number of HIV variants available for transmission and that the possible immunodominant nature of what may be protective anti-HIV T-cell responses suggest the need for HLA-based HIV subunit vaccines. HLA-based HIV vaccines are multivalent mixtures of immunogens reflecting the most common HIV variants in a particular geographic location. They would induce anti-HIV T-cell immunity by containing sufficient immunogenic cytotoxic T-lymphocyte (CTL) and T helper epitopes capable of binding to the HLA molecules expressed on antigen-presenting cells of individuals of the cohort to be vaccinated. The mixture of immunogens could range from a mixture of non-HIV vectors expressing HIV proteins to mixtures of HIV recombinant proteins and/or synthetic peptides.