Rectal and vaginal immunization with a macromolecular multicomponent peptide vaccine candidate for HIV-1 infection induces HIV-specific protective immune responses

An effective vaccine for human immunodeficiency virus (HIV) is needed to st imulate the immune response of the genital mucus to prevent mucosal transmi ssion of the virus. We have developed a macromolecular multicomponent pepti de vaccine candidate, VC1. Both rectal and vaginal immunization of VC1 mixe d with cholera toxin (CT) induced HIV-1-specific IgA antibody in mouse feca l extract solution and vaginal wash. These antibody productions were enhanc ed by the combination with IL-4 or GMCSF expressing plasmids. Either fecal extract or vaginal wash solution from immunized mice inhibited production o f HIV-1(IIIB) p24 protein. The mononuclear cells from spleen, intestinal ly mph nodes, or Peyer's patches from VC1-and CT-immunized mice released IFN-g amma or IL-4, when these cells were co-cultured with VC1 antigen. In additi on, the regional lymphoid cells from rectal and vaginal region of mice immu nized with VC1 and CT also elicited a substantial level of HIV-1-specific c ytotoxic T cell (CTL) response, This CTL response was enhanced by the addit ion of IL-12 expressing plasmid. Our results clearly demonstrated that both rectal and vaginal immunization could induce systemic and mucosal immuniti es specific for HIV-1. (C) 2000 Elsevier Science Ltd. All rights reserved.