Rapid appearance of secondary immune responses and protection from acute CD4 depletion after a highly pathogenic immunodeficiency virus challenge in macaques vaccinated with a DNA prime/Sendai virus vector boost regimen

Heterologous prime/boost regimens are AIDS vaccine candidates because of th eir potential for inducing cellular immune responses. Here, we have develop ed a prime/boost regimen leading to rapid control of highly pathogenic immu nodeficiency virus infection in macaques. The strategy, priming by an env a nd nef deletion-containing simian-human immunodeficiency virus (SHIV) provi ral DNA followed by a single booster with a Gag-expressing Sendai virus (Se V-Gag), efficiently induced virus-specific T cells, which were maintained f or more than 3 months until challenge. While all naive control macaques sho wed acute CD4(+) T-cell depletion at week 2 after an intravenous SHIV89.6PD challenge, all the macaques vaccinated with the prime/boost regimen were p rotected from depletion and showed greatly reduced peak viral loads compare d with controls. Vaccination with the DNA alone or SeV-Gag alone was not en ough to confer the consistent protection from the depletion, although it le d to efficient secondary CD8(+) T-cell responses at week 2 after challenge. At week 1, a difference in the secondary responses between the protected a nd the unprotected macaques was clear; rapid augmentation of virus-specific CD8(+) T cells was detected in the former but not in the latter. Thus, our results indicate the importance of rapid secondary responses for reduction in the peak viral loads and protection from acute CD4(+) T-cell depletion.