| Intranasal (i.n.) delivery of vaccines proved to be an effective route of immunization for induction of systemic and mucosal immune responses. This is important for vaccine development against pathogens that use mucosal sites as points of entry, such as HIV-1. Among the mechanisms of protection at mucosal surfaces, HIV-1-specific antibodies, especially of the IgA isotype, have the potential to neutralize the virus that initiates infection. Production of these antibodies in high titers, together with the generation of broadly neutralizing systemic antibodies, and cellular responses have been the central challenges of AIDS vaccine research. In the present study, I tested HIV-1 surface glycoproteins gp120 and gp140 as immunogens when administered i.n. to mice. IL-12 and cholera toxin subunit B (CTB) administration with HIV-1 immunogens induced HIV-1-specific antibody responses in both the systemic compartment and at mucosal sites of infection. While gp140 induced superior systemic and mucosal antibody responses than gp120, gp140-specific mucosal antibodies were inferior to gp120-induced antibodies in neutralizing HIV-1. To demonstrate that the respiratory antibodies were produced locally in the lung, mice received i.n. influenza vaccine or influenza vaccine plus IL-12. Mice receiving influenza vaccine plus IL-12 developed significantly higher levels of virus-specific total, IgG2a, and IgA spot forming cells (SFCs) in their lungs, compared with control mice. In addition, influenza vaccine and IL-12 generated organized lymphoid tissue in the lung and immunofluorescence analysis showed localized IgA and IgG production. IFN-γ KO (GKO) mice had higher numbers of total and IgA-producing cells than wild type animals, suggesting that cytokines other than IFN-γ were involved in the mucosal immune response. |
