BACKGROUND: 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. METHODS: We conducted a phase 1, dose-escalation, open-label trial of cAd3-EBO. Twenty healthy adults, in sequentially enrolled groups of 10 each, received vaccination intramuscularly in doses of 2×1010 particle units or 2×1011 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. RESULTS: In this small study, no safety concerns were identified; however, transient fever developed within 1 day after vaccination in two participants who had received the 2×1011 particle-unit dose. Glycoprotein-specific antibodies were induced in all 20 participants; the titers were of greater magnitude in the group that received the 2×1011 particle-unit dose than in the group that received the 2×1010 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 2×1011 particle-unit dose than among those who received the 2×1010 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 2×1011 particle-unit dose. CONCLUSIONS: 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. (Funded by the Intramural Research Program of the National Institutes of Health; VRC 207 ClinicalTrials.gov number, NCT02231866 .).
BACKGROUND: 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. METHODS: We conducted a phase 1, dose-escalation, open-label trial of cAd3-EBO. Twenty healthy adults, in sequentially enrolled groups of 10 each, received vaccination intramuscularly in doses of 2×1010 particle units or 2×1011 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. RESULTS: In this small study, no safety concerns were identified; however, transient fever developed within 1 day after vaccination in two participants who had received the 2×1011 particle-unit dose. Glycoprotein-specific antibodies were induced in all 20 participants; the titers were of greater magnitude in the group that received the 2×1011 particle-unit dose than in the group that received the 2×1010 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 2×1011 particle-unit dose than among those who received the 2×1010 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 2×1011 particle-unit dose. CONCLUSIONS: 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. (Funded by the Intramural Research Program of the National Institutes of Health; VRC 207 ClinicalTrials.gov number, NCT02231866 .).
Authors: Jason A Regules; John H Beigel; Kristopher M Paolino; Jocelyn Voell; Amy R Castellano; Zonghui Hu; Paula Muñoz; James E Moon; Richard C Ruck; Jason W Bennett; Patrick S Twomey; Ramiro L Gutiérrez; Shon A Remich; Holly R Hack; Meagan L Wisniewski; Matthew D Josleyn; Steven A Kwilas; Nicole Van Deusen; Olivier Tshiani Mbaya; Yan Zhou; Daphne A Stanley; Wang Jing; Kirsten S Smith; Meng Shi; Julie E Ledgerwood; Barney S Graham; Nancy J Sullivan; Linda L Jagodzinski; Sheila A Peel; Judie B Alimonti; Jay W Hooper; Peter M Silvera; Brian K Martin; Thomas P Monath; W Jay Ramsey; Charles J Link; H Clifford Lane; Nelson L Michael; Richard T Davey; Stephen J Thomas Journal: N Engl J Med Date: 2015-04-01 Impact factor: 91.245
Authors: Michel P M Vierboom; Agnes L Chenine; Patricia A Darrah; Richard A W Vervenne; Charelle Boot; Sam O Hofman; Claudia C Sombroek; Karin Dijkman; Mohamed A Khayum; Marieke A Stammes; Krista G Haanstra; Chantal Hoffmann; Doris Schmitt; Nathalie Silvestre; Alexander G White; H Jacob Borish; Robert A Seder; Nadia Ouaked; Stephane Leung-Theung-Long; Geneviève Inchauspé; Ravi Anantha; Mary Limbach; Thomas G Evans; Danilo Casimiro; Maria Lempicki; Dominick J Laddy; Aurelio Bonavia; Frank A W Verreck Journal: NPJ Vaccines Date: 2020-05-14 Impact factor: 7.344