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Vaccines against several pathogens have been developed using human-derived adenovirus vectors, and adenovirus-based Ebola virus (EBOV) vaccines have been shown to protect macaques (NEJM JW Infect Dis Sep 22 2003). However, preexisting immunity to adenoviruses can limit the effectiveness of such formulations. To circumvent this issue, researchers created monovalent (Zaire EBOV) and bivalent (Zaire EBOV and Sudan EBOV) vaccines using two chimpanzee adenovirus (ChAd) vectors. These vaccines were found to be protective for macaques challenged with a lethal dose of Zaire EBOV 5 weeks after immunization, although efficacy in preventing viremia and death varied by ChAd vector used and by vaccine dosage.
The ChAd monovalent vaccine, which performed better, was tested for durable immunity by challenging macaques with EBOV 10 months after immunization. Two of four animals receiving a high vaccine dose survived. Boosting with a second immunization 8 weeks after the first extended the protective immunity: One of three animals survived lethal challenge 10 months after a booster dose of monovalent ChAd vaccine, as did four of four that received a booster of modified vaccinia EBOV vaccine. In vitro work showed that at the time of challenge, levels of interferon- and tumor necrosis factor–coproducing effector cells and triple-cytokine–producing CD8 cells were higher in ChAd/vaccinia-immunized animals than in ChAd/ChAd-immunized ones.
Stanley DA et al. Chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge. Nat Med 2014 Sep 7; [e-pub ahead of print]. (http://dx.doi.org/10.1038/nm.3702)
Comment
These findings provide support for immediate human testing of this ChAd-based monovalent EBOV vaccine, which might help in controlling outbreaks. However, we cannot predict the vaccine's effectiveness against an EBOV strain that undergoes substantial evolution during an outbreak. Furthermore, the necessity of boosting with a second vaccine formulation to produce durable immunity will make long-term protection of at-risk populations more complex.