INFECTION OF VAGINAL AND COLONIC EPITHELIAL-CELLS BY THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IS NEUTRALIZED BY ANTIBODIES RAISED AGAINST CONSERVED EPITOPES IN THE ENVELOPE GLYCOPROTEIN GP120

The rectal and genital tract mucosae are considered to be major sites of entry for the human immuno-deficiency virus (HIV) during sexual contact. We now demonstrate that vaginal epithelial cell can be infected by HIV type 1 (HIV-1) via a mechanism similar to that described for neuroglial cells and, more recently, for colorectal epithelial cells, involving initial interaction of the HIV-1 envelope glycoprotein gp120 with a cell-surface glycosphingolipid (sulfated lactosylceramide). A hyperimmune serum against gp120 was able to neutralize HIV-1 infection of vaginal epithelial cells. Site-directed immunization was employed to identify sites on gp120 recognized by antibodies neutralizing HIV-1 infection of vaginal colonic epithelial cells. Hyperimmune sera were raised in monkeys against a series of 40 overlapping synthetic peptides covering the entire sequence of HIV-1 (HTLV-IIIB) gp120. Antisera raised against five synthetic peptides, corresponding to three relatively conserved regions and to the hypervariable region (V3 loop), efficiently neutralized HIV-1 infection of human vaginal epithelial cells in vitro. Similar results were obtained with the colonic cells. Hyperimmune sera to all five peptides have been shown earlier to neutralize HIV-1 infectivity in CD4(+) T cells. These results have obvious implications for the design of mucosal subunit vaccines against sexually transmitted HIV-1 infections.