SciCombinator

Discover the most talked about and latest scientific content & concepts.

Chimpanzee Adenovirus Vector Ebola Vaccine - Preliminary Report

OPEN The New England journal of medicine | 27 Nov 2014

JE Ledgerwood, AD DeZure, DA Stanley, L Novik, ME Enama, NM Berkowitz, Z Hu, G Joshi, A Ploquin, S Sitar, IJ Gordon, SA Plummer, LA Holman, CS Hendel, G Yamshchikov, F Roman, A Nicosia, S Colloca, R Cortese, RT Bailer, RM Schwartz, M Roederer, JR Mascola, RA Koup, NJ Sullivan and BS Graham
Abstract
Background The unprecedented 2014 epidemic of Ebola virus disease (EVD) has 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 2×10(10) particle units or 2×10(11) particle units. Primary and secondary end points related to safety and immunogenicity were assessed throughout the first 4 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 2×10(11) particle-unit dose. Glycoprotein-specific antibodies were induced in all 20 participants; the titers were of greater magnitude in the group that received the 2×10(11) particle-unit dose than in the group that received the 2×10(10) particle-unit dose (geometric mean titer against the Zaire antigen, 2037 vs. 331; P=0.001). Glycoprotein-specific T-cell responses were more frequent among those who received the 2x10(11) particle-unit dose than among those who received the 2×10(10) 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). Conclusions Reactogenicity and immune responses to cAd3-EBO vaccine were dose-dependent. At the 2×10(11) 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. Clinical trials assessing cAd3-EBO are ongoing. (Funded by the Intramural Research Program of the National Institutes of Health; VRC 207 ClinicalTrials.gov number, NCT02231866 .).
Tweets*
74
Facebook likes*
27
Reddit*
2
News coverage*
30
Blogs*
3
SC clicks
0
Concepts
Vaccination, Western Red Colobus, T helper cell, Immunity, Immunology, Ebola, Antibody, Immune system
MeSH headings
-
comments powered by Disqus

* Data courtesy of Altmetric.com