MUCOSAL MODEL OF GENITAL IMMUNIZATION IN MALE RHESUS MACAQUES WITH A RECOMBINANT SIMIAN IMMUNODEFICIENCY VIRUS P27 ANTIGEN

Human immunodeficiency virus (HIV) can be transmitted through infected seminal fluid or vaginal or rectal secretions during heterosexual or homosexual intercourse. To prevent mucosal transmission and spread to the regional lymph nodes, an effective vaccine may need to stimulate i mmune responses at the genitourinary mucosa. In this study, we have de veloped a mucosal model of genital immunization in male rhesus macaque s, by topical urethral immunization with recombinant simian immunodefi ciency virus p27(gag), expressed as a hybrid Ty virus-like particle (T y-VLP) and covalently linked to cholera toxin B subunit. This treatmen t was augmented by oral immunization with the same vaccine but with ad ded killed cholera vibrios. Polymeric secretory immunoglobulin A (sIgA ) and IgG antibodies to p27 were induced in urethral secretions, urine , and seminal fluid. This raises the possibility that the antibodies m ay function as a primary mucosal defense barrier against SIV (HIV) inf ection. The regional lymph nodes which constitute the genital-associat ed lymphoid tissue contained p27-specific CD4(+) proliferative and hel per T cells for antibody synthesis by B cells, which may function as a secondary immune barrier to infection. Blood and splenic lymphocytes also showed p27-sensitized CD4(+) T cells and B cells in addition to s erum IgG and IgA p27-specific antibodies; this constitutes a third lev el of immunity against dissemination of the virus. A comparison of gen ito-oral with recto oral and intramuscular routes of immunization sugg ests that only genito-oral immunization elicits specific sIgA and IgG antibodies in the urine, urethra, and seminal fluid. Both genito-oral and recto-oral immunizations induce T-cell and B-cell immune responses in regional lymph nodes, with preferential IgA antibody synthesis. Th e mucosal route of immunization may prevent not only virus transmissio n through the genital mucosa but also dissemination and latency of the virus in the draining lymph nodes.