Infection with HIV-1 is characterized by a decrease on function and number of CD4+ T cells which are required for helper function in the antibody response to protein antigens. We have previously shown that antibody responses to HIV-1 proteins in mice are T-helper cell dependent, whereas HIV proteins and peptides, conjugated to Brucella abortus (BA) do not require CD4+ T cells. Subsequently, we conjugated an 18 amino acid peptide (N3V3) derived from the third variable region of HIV-MN envelope, containing both B and CTL epitopes, to BA (N3V3-BA) and to keyhole limpet hemocyanin (N3V3-KLH). N3V3-BA was able to induce anti-peptide antibody and CTL responses in intact mice and, in contrast to N3V3-KLH, was effective in mice depleted of CD4+ T cells. Since the greatest increase in HIV-1 transmission is occurring by heterosexual transmission we considered it important to determine whether we could induce mucosal immunity against HIV-1. Mice immunized with N3V3-BA were found to develop serum and mucosal anti-peptide antibodies of the IgA subclass in serum and at mucosal surfaces. This was also found in MHC class II knock-out mice, that lack functional T-helper cell. This approach has been also tried in Rhesus macaques. Two monkeys immunized by the intramuscular route with N3V3-BA developed high titer anti-peptide antibodies capable of neutralizing HIV-1 in vitro. Furthermore, these monkeys secreted peptide-specific IgG and IgA at mucosal surfaces. These results indicate that B. abortus can be used as a carrier in the development of subunit vaccines designed to generate anti-HIV antibody mucosal responses in individuals with impaired CD4+ T cell function. This could reduce transmission of virus from infected persons by sexual contact and by mothers to their newborns. In a separate set of experiments we demonstrated that co-administration of Brucella abortus (a strong Th1 type cytokine inducer) with allergen, ovalbumin + alum, resulted in an increase of anti-ova IgG2a and a decrease in IgE. This has important implications in reducing allergic responses.
