In previous preclinical trials, we achieved significant systemic and mucosal T-cell responses after rectal, nasal, vaginal, oral and intestinal immunizations with SIV or SHIV DNA combined with SIV- or SHIV-MVA and observed some level of protection, particularly in terms of delayed CD4+ T-cell loss and preservation of the Th17/Treg ratio, but also as significantly higher number of vaginal challenges required to achieve infection (56, 73, 74, 79, 80). Here, CD4 is linked to infection.