Immunostimulatory DNA-based vaccines elicit multifaceted immune responses against HIV at systemic and mucosal sites

Immunostimulatory DNA sequences (ISS, also known as CpG motifs) are pathoge n-associated molecular patterns that are potent stimulators of innate immun ity. We tested the ability of ISS to act as an immunostimulatory pathogen-a ssociated molecular pattern in a model HIV vaccine using gp120 envelope pro tein as the Ag. Mice immunized with gp120 and ISS, or a gp120:ISS conjugate , developed gp120-specific immune responses which included: 1) Ab productio n; 2) a Th1-biased cytokine response; 3) the secretion of beta -chemokines, which are known to inhibit the use of the CCR5 coreceptor by HIV; 4) CTL a ctivity; 5) mucosal immune responses; and 6) CD8 T cell responses that were independent of CD4 T cell help. Based on these results, ISS-based immuniza tion holds promise for the development of an effective preventive and thera peutic HIV vaccine.