Strong Vaccine-Elicited Th1-Biased CD4 T cell Response Abrogates SIV Vaccine Efficacy

Results from the Step trial in humans and studies in non-human primates highlighted a role for heightened activated CD4 T cell response in promoting HIV/SIV acquisition. However, the contribution of vaccine-specific CD4 T cell response in influencing protection is not known. Here, using the macaque model, we show that vaccine-induced Th1-biased CCR5+ CD4 T cell response in blood and mucosal tissue above a certain thresh¬old is detrimental for vaccine-mediated protection against pathogenic mucosal SIV infections. 10 vaccinated animals that acquired SIV infection within the first two challenges (early SIV acquirers) and 12 vaccinated animals that acquired SIV infection after 6 challenges (late SIV acquirers). We performed microarray analysis on whole blood samples for both set of animals at multiple days after the 1st DNA vaccine (Wk0), 1st MVA boost (Wk16), 2nd MVA boost (Wk32) and 1st rectal challenge.