215 The A1 subunit of Cholera toxin as an adjuvant for HIV DNA vaccines

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Excerpt

Vaccination using plasmid DNA remains a promising means to develop effective prophylactic and therapeutic vaccines against HIV. Unfortunately, their poor immunogenicity in primates demands the use of genetic adjuvants and/or improved delivery techniques. Our approach is to exploit adjuvants, such as the A1 domain of cholera toxin (CTA1), that directly activate dendritic cells. Using SIV gag and HIV gp120 as model antigens in mouse studies, we found that the adjuvanticity of CTA1 is modulated significantly by dose, route (i.m. vs Gene Gun vs electroporation), frequency (1, 2, 3 doses), and type of antigen administered. When delivered via Gene Gun in Cynomolgus macaques, a CTA1 adjuvanted DNA prime significantly enhanced (>10-fold) for a SIV gag humoral response after boosting with a recombinant SIV gag protein. We continue to evaluate CTA1 with additional immunogens to determine if the adjuvanticity diminishes with each subsequent use.

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