OA04.04
Background: Growing evidence suggests that NK cells and antibodies that mediate ADCC can control HIV infection. ADCC was shown to have an inverse correlation with risk of HIV infection in the RV144 vaccine trial that showed 31% protection from HIV acquisition. We recently showed the recruitment of CD16+ NKG2A+ NK cells to the gut during ALVAC/SIV/gp120 vaccine regimen in macaques. Here we investigated whether NKG2A+ NK cells together with vaccine induced anti-envelop IgG at mucosa can protect from SIVmac251 acquisition.
Methods: IgG was purified from sera following 8 additional immunizations with ALVAC-SIV/gp120/Alum of 8 macaques previously exposed to SIVmac251 remaining uninfected. To demonstrate that systemically given IgG can localize to the gut, CY5 labeled anti-human IgG was subcutaneously administered to macaques and anti-human antibodies were measured in serum and rectum by ELISA and immunohistochemistry (IHC) at 6h, 24h and weekly for 4 weeks. Two macaque cohorts (A and B) were vaccinated with ALVAC-SIV (SIV766 Gag-Pro gp120TM) at 0, 4, 12 and 24 weeks. ALUM was administered together with the vaccine at 12 and 24 weeks. Purified IgG will be given to group A (n=8) subcutaneously (24h) and intra-rectally (IR) (2h) prior to the repeated low dose challenge with SIVmac251 IR in July 2014. Group B (n=8) and unvaccinated group (n=12) will be challenged simultaneously.
Results: Purified IgG from 8 protected animals showed 1.87% of gp120 specific activity by ELISA. Anti-human IgG was detected in serum and rectal biopsies by ELISA and IHC up to 3 weeks post antibody administration. Cytometric analysis of rectal biopsies showed recruitment of NKG2A+NK (p=0.03) cells to the gut of vaccines.
Conclusions: Our current data shows the recruitment of NKG2A+NK cells to the gut and successful delivery of antibodies to the gut mucosa. Protection after SIV challenge in the end of July 2014, will confirm our hypotheses that the vaccine mediated recruitment of NK cell together with antibodies can prevent SIV acquisition.
