View All Abstracts for Session 42
232 Cytokine Adjuvants for the Induction of Anti-HIV Mucosal IgA and Cell-Mediated Immune Responses
H. Staats*, T. Tlusty, G. Sempowski, H.-X. Liao, and B. Haynes
Duke Univ. Med. Ctr., Durham, NC, USA
Vaccine-induced HIV-specific mucosal immune responses, both secretory IgA and cell-mediated immune responses, may be required for protection against mucosally transmitted HIV. Induction of antigen-specific immunity after mucosal immunization requires the use of mucosal adjuvants. Mucosal adjuvants currently used include cholera toxin (CT), labile toxin (LT), and their mutated, detoxified derivatives. Adverse effects associated with the use of toxins as mucosal adjuvants may prevent their use in humans. Studies in our lab have evaluated proinflammatory cytokines for use as safe alternatives to toxin mucosal adjuvants with HIV vaccines. Female BALB/c mice were nasally immunized with an HIV immunogen +/( cytokine adjuvants on days 0, 7, 14, and 28, and mucosal and systemic humoral and cell-mediated immune responses were monitored at day 35. Nasal immunization with an HIV immunogen derived from the SHIV 89.6P virus formulated with a combination of IL-1alpha, IL-12, and IL-18 induced serum anti-HIV IgG1 and IgA geometric mean titers of 1:131,072 and 1:7,131, respectively. This immunization protocol also induced anti-HIV IgA geometric mean titers of 1:1,176, 1: 7,131, and 1:4,705 in the saliva, fecal extracts, and vaginal lavage, respectively, by day 35. Nasal immunization with peptide alone did not induce detectable serum or mucosal anti-HIV antibody responses (p < 0.05, peptide vs. peptide + cytokines). In another study, nasal immunization with an HIV immunogen from the IIIB strain of HIV and IL-1alpha, IL-12 plus GM-CSF induced HIV-specific IFN-gamma?secreting cells in the cervical lymph node, lung, and spleen with 311.9 +/( 56.8, 318.3 +/( 145.2, and 356 +/( 50.9 IFN-gamma spot-forming cells (SFC)/106 cells, respectively. Mice immunized with peptide only had < 3 IFN-gamma SFC/106 cells (p < 0.01 peptide only vs. peptide + cytokines). Our results indicate that proinflammatory cytokines may be used as mucosal adjuvants for the induction of systemic and mucosal IgA and cell-mediated immune responses when nasally administered with HIV immunogens.
Contact Author about this Abstract
