Chimpanzee adenovirus plus#

We identified ChAd3 and ChAd63 as potential candidate vaccine vectors on the basis of their low neutralization by human sera, genetic distance from poor-efficacy alternative vectors 8 and lack of replication in the vaccine recipient (a potential drawback of replicating vaccine vectors such as vesicular stomatitis virus (VSV)) 15, as well as the protection conferred by a ChAd63 vaccine against malaria 12.

Chimpanzee adenovirus plus#

Here we evaluated monovalent (EBOV GP) or bivalent (EBOV plus Sudan ebolavirus (SUDV) GPs) ChAd- and MVA-vectored ebolavirus vaccines for immunogenicity, protection against acute EBOV challenge and durable protection using single-inoculation and prime-boost approaches. ChAds have been evaluated as vaccine vectors in mice 6, 10, nonhuman primates (NHPs) 12 and human clinical trials 5, 13, 14 have low worldwide seroprevalance 6, 10 and are not cross-neutralized by human anti-adenovirus sera 6. Adenoviruses isolated from nonhuman sources including chimpanzees and apes 10 may overcome this limitation, and they have shown promise for EBOV protection, but only against a modified virus in mice 11. However, human-derived rAd vectors are limited by preexisting immunity to the vectors. rAd5 EBOV vaccines protect against acute EBOV challenge (4 weeks after vaccination), whereas EBOV vaccines using alternative human adenoviruses do not 8, perhaps owing to differences in antigen expression 6 or target cell receptor preference 9. For ebolavirus, rAd vaccines that confer protection against acute EBOV challenge generate effector CD8 + T cell responses within 3 weeks of immunization 7 and therefore have the potential to provide rapid immunity in an acute human outbreak setting. Human-derived rAd vectors have undergone extensive development in preclinical and human trials as vaccines for multiple pathogens 1, 2, 3, 4, 5, 6.