T-CELL AND B-CELL FUNCTIONS AND EPITOPE EXPRESSION IN NONHUMAN-PRIMATES IMMUNIZED WITH SIMIAN IMMUNODEFICIENCY VIRUS-ANTIGEN BY THE RECTAL ROUTE

Transmission of human immunodeficiency virus (HIV) in North America an d Europe occurs most commonly through the rectal mucosa during homosex ual intercourse. The simian immunodeficiency virus (SIV) macaque model has been used to investigate rectal immunization. The vaccine used wa s a recombinant SIV gag p27 expressed as hybrid Ty virus-like particle s (Ty-VLP). Sequential ororectal (OR) mucosal immunization was compare d with i.m. immunization. Whereas both routes of immunization induced serum IgA and IgG p27 antibodies, only OR immunization induced rectal secretory IgA antibodies. Specific CD4+ T-cell proliferative responses to stimulation with p27 were found after i.m. immunization only in th e blood and spleen, but after OR immunization they were found in the i nternal iliac and inferior mesenteric lymph nodes in addition to the b lood and spleen. T-cell epitope mapping of the proliferative responses of short-term cell lines (STCLs) grown from peripheral blood or lymph oid cells revealed a major epitope within the polypeptide 121-150 afte r either route of immunization. Two minor T-cell epitopes were found w ithin peptide 41-80 in STCLs from splenic and circulating cells. B-cel l epitope mapping of serum or biliary IgA and IgG antibodies revealed two overlapping or adjacent immunodominant epitopes to the T-cell epit opes within the polypeptides 121-170 and 51-90. The results suggest th at rectal augmented by oral immunization with a recombinant particulat e antigen in nonhuman primates elicits secretory IgA and to a lesser e xtent IgG responses in the draining lymph nodes and the rectal mucosa, whereas systemic immunization targets predominantly splenic and circu lating T- and B-cell responses. These findings may have important impl ications in the strategy of designing vaccines in prevention of homose xual transmission of HIV infection.