Innate and adaptive mucosal immunity in protection against HIV infection.

Control of the HIV pandemic requires an effective vaccine. The difficulties in developing a preventive vaccine are generally believed to be due to the rapid rate of mutation of HIV that escapes cytotoxic lymphocytes (CTL) and the problems in induction of neutralising antibodies to wild strains of HIV. These difficulties should re-orientate vaccine strategy into four somewhat neglected areas of immunisation. Innate immunity, with its rapid protective response to infection that is independent of memory and relies on an optimal mucosal adjuvant. Targeting the genital and rectal mucosa, with the associated lymph nodes, as an immune response has to be elicited directly on encountering HIV during sexual intercourse. Stimulating a broadly based adaptive immune response that enhances the memory CD4(+) and CD8(+) T cells and B cells, induces maturation of dendritic cells and results in Th1 polarised immunity. Taking advantage of "experiments of nature", by utilising host antigens, as manifested by protection against HIV infection in homozygous Delta32 CCR5 individuals and in allo-immunity.