A Monovalent XXXX Adenovirus Ebola Vaccine Boosted with MVA.

@entity1 @entity2598 @entity8310 @entity831 @entity39996 @entity204
UNASSIGNED: Background The West African outbreak of @entity2598 that peaked in 2014 has caused more than 11,000 @entity204 . The development of an effective Ebola vaccine is a priority for control of a future outbreak. Methods In this phase 1 study, we administered a single dose of the @entity831 adenovirus 3 (ChAd3) vaccine encoding the surface glycoprotein of @entity39996 ( @entity39996 ) to 60 healthy adult volunteers in Oxford, United Kingdom. The vaccine was administered in three dose levels - 1*10(10) viral particles, 2.5*10(10) viral particles, and 5*10(10) viral particles - with 20 @entity1 in each group. We then assessed the effect of adding a booster dose of a modified vaccinia Ankara (MVA) strain, encoding the same Ebola virus glycoprotein, in 30 of the 60 @entity1 and evaluated a reduced prime-boost interval in another 16 @entity1 . We also compared antibody responses to inactivated whole Ebola virus virions and neutralizing antibody activity with those observed in phase 1 studies of a recombinant @entity8310 virus-based vaccine expressing a @entity39996 glycoprotein (rVSV- @entity39996 ) to determine relative potency and assess durability. Results No safety concerns were identified at any of the dose levels studied. Four weeks after immunization with the ChAd3 vaccine, ZEBOV-specific antibody responses were similar to those induced by rVSV- @entity39996 vaccination, with a geometric mean titer of 752 and 921, respectively. @entity39996 neutralization activity was also similar with the two vaccines (geometric mean titer, 14.9 and 22.2, respectively). Boosting with the MVA vector increased virus-specific antibodies by a factor of 12 (geometric mean titer, 9007) and increased glycoprotein-specific CD8+ T cells by a factor of 5. Significant increases in neutralizing antibodies were seen after boosting in all 30 @entity1 (geometric mean titer, 139; P<0.001). Virus-specific antibody responses in @entity1 primed with ChAd3 remained positive 6 months after vaccination (geometric mean titer, 758) but were significantly higher in those who had received the MVA booster (geometric mean titer, 1750; P<0.001). Conclusions The ChAd3 vaccine boosted with MVA elicited B-cell and T-cell immune responses to @entity39996 that were superior to those induced by the ChAd3 vaccine alone. (Funded by the Wellcome Trust and others; ClinicalTrials.gov number, NCT02240875 .).
