P19-46. Co-delivery of mucosal chemokine plasmids in a systemically delivered DNA vaccine elicits systemic and mucosal immune responses in mice and macaques

Abstract

Results Mice: Co-immunization with chemokines induced significant enhancement of HIV-1 specific CD8+ T cell IFNgamma secretion in the periphery and TNF-alpha, IL-2 and IFN-gamma by gut lymphocytes. Co-immunization with mucosal chemokines augmented HIV-1-specific sIgA in sera/fecal samples. Similar immunogenicity data was observed to Influenza A/PR8/34 hemagglutanin plasmid including responses that neutralized virus and protected mice from morbidity/mortality associated with lethal mucosal challenge. Macaque: In the periphery, we observed significant IFN-gamma in all groups (~6,000 SFU each). However intracellular cytokine staining on mucosal lymphocytes showed a trend toward an increase in CD8+T cells secreting TNF and IL-2 in CCL27 coimmunized macaques, levels greater than those observed in infected animals. Enhanced antigen-specific IgA was also detected in sera of chemokine-vaccinated macaques. A mucosal challenge is scheduled to determine if the functionality and phenotype of vaccine-induced immunity, either at the mucosa or periphery, is a driving determinant of protection.