Target Health Blog

Chimpanzee Adenovirus Vector Ebola Vaccine

March 13, 2017

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Tropical Medicine
Source:

The unprecedented 2014 epidemic of Ebola virus disease (EVD) prompted an international response to accelerate the availability of a preventive vaccine. A replication-defective recombinant chimpanzee adenovirus type 3-vectored ebolavirus vaccine (cAd3-EBO), encoding the glycoprotein from Zaire and Sudan species, that offers protection in the nonhuman primate model, was rapidly advanced into phase 1 clinical evaluation.

As a result, in a study published in the New England of Medicine (2017; 376:928-938), enrolled 20 healthy adults, in sequentially enrolled groups of 10 each, received vaccination intramuscularly in doses of 2x1010 particle units or 2x1011 particle units. Primary and secondary end points related to safety and immunogenicity were assessed throughout the first 8 weeks after vaccination; in addition, longer-term vaccine durability was assessed at 48 weeks after vaccination.

While no safety concerns were identified, transient fever developed within 1 day after vaccination in two participants who had received the 2x1011 particle-unit dose. Glycoprotein-specific antibodies were induced in all 20 participants; the titers were of greater magnitude in the group that received the 2x1011 particle-unit dose than in the group that received the 2x1010 particle-unit dose (geometric mean titer against the Zaire antigen at week 4, 2037 vs. 331; P=0.001). Glycoprotein-specific T-cell responses were more frequent among those who received the 2x1011 particle-unit dose than among those who received the 2x1010 particle-unit dose, with a CD4 response in 10 of 10 participants versus 3 of 10 participants (P=0.004) and a CD8 response in 7 of 10 participants versus 2 of 10 participants (P=0.07) at week 4. Assessment of the durability of the antibody response showed that titers remained high at week 48, with the highest titers in those who received the 2?1011particle-unit dose.

According to the authors, reactogenicity and immune responses to cAd3-EBO vaccine were dose-dependent. At the 2?1011 particle-unit dose, glycoprotein Zaire-specific antibody responses were in the range reported to be associated with vaccine-induced protective immunity in challenge studies involving nonhuman primates, and responses were sustained to week 48. Phase 2 studies and efficacy trials assessing cAd3-EBO are in progress.

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