An optimized SIV DNA vaccine can serve as a boost for Ad5 and provide partial protection from a high-dose SIVmac251 challenge

► Optimized DNA can serve as an effective boost following a robust Ad5 vector prime. ► Ad5-prime DNA-boost improved challenge control following SIVmac251 challenge. ► Control of SIV correlated with the expansion of HLA-DR+ CD8+ effector T-cells.