The male and female genital tracts are served by a local immune system that displays features distinguishing them from other mucosal sites. In contrast to the intestinal tract, where locally produced IgA is the dominant Ig, secretions of the male and female genital tract contain predominantly IgG of both local and systemic origin. Genital tract tissues also lack mucosal lymphoepithelial inductive sites analogous to intestinal Peyer's patches; consequently, local immunization or infections with sexually transmitted pathogens induce low immune responses. Human immunodeficiency virus 1 (HIV-1) infection must be primarily considered as a mucosal disease with extensive involvement of the systemic immune compartment. Although the majority of infections are acquired through the genital mucosa, a high rate of virus replication and profound CD4 + T cell depletion occurs in the intestinal mucosa and other mucosal tissues shortly after infection. Evaluation of HIV-specific antibodies in sera and external secretions, including vaginal washes and semen, unexpectedly revealed a selective lack of IgA responses. Moreover, specific antibody-secreting cells in peripheral blood were of the IgG isotype, even in mucosally infected individuals. Whether humoral responses to previously or newly encountered antigens are compromised in HIV-1-infected persons is under current investigation.

To address an existing controversy concerning the presence of HIV-1-specific antibodies of the IgA isotype in the female genital tract secretions of highly-exposed but persistently seronegative (HEPSN) women, 41 samples of plasma and cervicovaginal lavage (CVL) fluid were distributed to six laboratories for their blinded evaluation using ELISA with 10 different

The mucosal immune response to HIV weighs in heavily on the battle against it, as the majority of infections occur via the mucosal route. The antibody response in the mucosae, specifically the genital tract, is characterized by binding and, in some studies, neutralizing HIV-specific IgG and IgA antibodies. Ample evidence, however, points to discrepancies and difficulties in the detection of HIV-specific IgA in HIV-positive subjects, and an even more pronounced divide surfaces in studies done with individuals exposed to HIV, but uninfected. Reports in the literature detail HIV-specific (in some cases, neutralizing) IgA antibodies, in the absence of specific IgG, in the serum and mucosal secretions of virus-exposed, seronegative subjects; this has given rise to speculation that HIV-specific IgA provides a protective immune response to the virus in high-risk individuals who remain seronegative. Contradictory results, however, describe the absence of both IgA and IgG HIV antibodies in the mucosal secretions of similar cohorts. Considering the importance of the antibody response to ascertaining the correlates of HIV immunity, as well as on vaccine research and development, this review addresses the relevant studies and their implications.

T4 DNA ligase catalyzes the template-dependent ligation of DNA. Using T4 DNA ligase under specific experimental conditions, we demonstrate that each of the four canonical nucleosides, centrally located on a template molecule such that they flank the site of ligation, can direct the ligation of nucleic acids regardless of the identity of the terminal nucleosides being covalently joined. This universal templating capability extends to those positions adjacent to the ligation junction. This is the first report, irrespective of the ligation method used or the identity of the template nucleosides (including analogs), which shows that nucleosides can act essentially as universal templates at ligation junctions in vitro. The canonical nucleosides do, however, differ in their ability to template sequence- independent ligations, with thymidine and guanosine being equally effective, yet more effective than adenosine and cytidine. Results indicate that hybridization strength surrounding the ligation junction is an important factor. The implications of this previously undiscovered property of T4 DNA ligase with canonical nucleosides are discussed.

Mucosal tissues of the genital tracts and the distal intestinal tract are portals of entry for infectious agents of sexually transmitted diseases, including HIV-1. Although the genital and intestinal tracts share a common embryologic origin and remain in anatomical proximity, these two sites display remarkably different immunologic features, including the levels, isotypes and molecular forms of immunoglobulins, and magnitudes and qualities of humoral and cellular immune responses. Thus, viral and bacterial infections of the genital tract or intravaginal immunizations induce, in the absence of mucosal adjuvants, minimal immune responses. Consequently, to induce relevant immune responses in the genital tract, alternative immunization routes have been explored, including systemic, intranasal, oral, or rectal immunization and their combinations. In limited studies performed in animals, systemic immunization with a subsequent mucosal (intranasal) immunization proved to be effective in the induction of humoral immune responses in genital tract secretions. The approaches have been explored to a limited extent in humans.