OA24.01
Background: The use of cytokine gene adjuvants to tailor the immune response is a strength of EP DNA vaccination. This has been established through the recent HVTN080 trial which demonstrated the potency of IL-12 with EP delivered DNA to drive T cell responses. However, for an HIV vaccine it is important to also induce strong humoral responses. To address the possible role of serum and vaginal IgA in HIV acquisition we utilized an adjuvanted DNA vaccine previously shown to drive IgA induction in a non-human primate vaginal challenge model.
Methods: Groups of 5 Indian rhesus macaques received a pSIVmac239 gag/pol and pSIVe660 gp120 alone, or with plasmids - pCCL25 (TECK), pCCL27 (CTACK) or pCCL28 (MEC), genetic adjuvants, at weeks 0, 6, 12, 18 and 48. Animals were challenged with 500 TCID SIVsmE660 intravaginaly twice a week for two weeks for 4 challenges.
Results: We observed higher vaginal IgA titers in gene adjuvanted animals compared with DNA vaccine alone. Following challenge, we observed an overall protection rate of 68% for all vaccinated animals. However, this protection rate was different for each vaccination regiment. Animals vaccinated with CCR10Ls, (CCL27 and CCL28,) exhibited robust control of set point viremia and chronic viremia (p<0.05) with 89% of animals controlling infection compared with only 40% in unadjuvanted animals and 14% in naïve challenge controls. However, CCR9L (CCL25) vaccinated animals resisted challenge in 60% of animals. Irrespective of vaccine group, animals that controlled viremia had the highest vaginal IgA and IgG levels post-vaccination.
Conclusions: Inclusion of immune plasmid adjuvants encoding mucosal chemokines in EP DNA vaccine regiments can improve challenge outcomes. Collectively these adjuvant approaches likely have importance for the development of next generation DNA vaccines and the data illuminates the need for continued research into the role of vaginal antibodies and protection from viral infection in NHP models.
