CD8+ cellular immunity mediates rAd5 vaccine protection against Ebola virus infection of nonhuman primates

Vaccines that protect nonhuman primates from lethal Ebola virus infection have been developed, but their protective mechanisms have not been clearly delineated. Nancy Sullivan et al . now report that the protective efficacy of a recombinant Ad5-based Ebola virus vaccine relies primarily on CD8 + T cells rather than on antibodies. The findings suggest that clinical development of T cell–based vaccines against Ebola virus is warranted. Vaccine-induced immunity to Ebola virus infection in nonhuman primates (NHPs) is marked by potent antigen-specific cellular and humoral immune responses 1 , 2 ; however, the immune mechanism of protection remains unknown. Here we define the immune basis of protection conferred by a highly protective recombinant adenovirus virus serotype 5 (rAd5) encoding Ebola virus glycoprotein (GP) 1 , 3 in NHPs. Passive transfer of high-titer polyclonal antibodies from vaccinated Ebola virus–immune cynomolgus macaques to naive macaques failed to confer protection against disease, suggesting a limited role of humoral immunity. In contrast, depletion of CD3 + T cells in vivo after vaccination and immediately before challenge eliminated immunity in two vaccinated macaques, indicating a crucial requirement for T cells in this setting. The protective effect was mediated largely by CD8 + cells, as depletion of CD8 + cells in vivo using the cM-T807 monoclonal antibody (mAb), which does not affect CD4 + T cell or humoral immune responses, abrogated protection in four out of five subjects. These findings indicate that CD8 + cells have a major role in rAd5-GP–induced immune protection against Ebola virus infection in NHPs. Understanding the immunologic mechanism of Ebola virus protection will facilitate the development of vaccines for Ebola and related hemorrhagic fever viruses in humans.