Evidence for early local viral replication and local production of antiviral immunity upon mucosal simian-human immunodeficiency virus SHIV89.6 infection in Macaca nemestrina

Transmission of human immunodeficiency virus type 1 (HIV-1) is largely a re sult of heterosexual exposure, leading many investigators to evaluate mucos al vaccines for protection against intravaginal (i.vag.) transmission in ma caque models of AIDS. Relatively little is known, however, about the dynami cs of viral replication and the ensuing immune response following mucosal i nfection. We have utilized a simian-human immunodeficiency virus (SHIV) to study the differences in viremia, CD4 T-cell percentages, and mucosal and s ystemic anti-SHIV Immoral and cellular immune responses during primary infe ction of animals infected either intravenously (i.v.) or i.vag. Positive vi ral cocultures, peripheral blood mononuclear cell viral load peaks, and CD4 cell declines were delayed by 1 week in the i.vag. inoculated animals comp ared to the animals infected i.v., demonstrating delayed viral spreading to the periphery. In contrast, mucosal anti-SHIV antibody levels were greater in magnitude and arose more rapidly and mucosal CD8(+) T-cell responses we re enhanced in the i.vag. group animals, whereas both the magnitudes and ti mes of onset of systemic immune responses for the animals in the two groups did not differ. These observations demonstrate that compartmentalization o f viral replication and induction of local antiviral immunity occur in the genital tract early after i.vag. but not i.v. inoculation. Induction of muc osal immunity to target this local, contained replication should be a goal in HIV vaccine development.