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A Monovalent Chimpanzee Adenovirus Ebola Vaccine Boosted with MVA.

ABSTRACT: BACKGROUND:The West African outbreak of Ebola virus disease that peaked in 2014 has caused more than 11,000 deaths. 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 chimpanzee adenovirus 3 (ChAd3) vaccine encoding the surface glycoprotein of Zaire ebolavirus (ZEBOV) 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 participants 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 participants and evaluated a reduced prime-boost interval in another 16 participants. 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 vesicular stomatitis virus-based vaccine expressing a ZEBOV glycoprotein (rVSV-ZEBOV) 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-ZEBOV vaccination, with a geometric mean titer of 752 and 921, respectively. ZEBOV 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 participants (geometric mean titer, 139; P<0.001). Virus-specific antibody responses in participants 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 ZEBOV that were superior to those induced by the ChAd3 vaccine alone. (Funded by the Wellcome Trust and others; ClinicalTrials.gov number, NCT02240875.).

SUBMITTER: Ewer K

PROVIDER: S-EPMC5798586 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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A Monovalent Chimpanzee Adenovirus Ebola Vaccine Boosted with MVA.

Ewer Katie K Ewer Katie K Rampling Tommy T Venkatraman Navin N Bowyer Georgina G Wright Danny D Lambe Teresa T Imoukhuede Egeruan B EB Payne Ruth R Fehling Sarah Katharina SK Strecker Thomas T Biedenkopf Nadine N Krähling Verena V Tully Claire M CM Edwards Nick J NJ Bentley Emma M EM Samuel Dhanraj D Labbé Geneviève G Jin Jing J Gibani Malick M Minhinnick Alice A Wilkie Morven M Poulton Ian I Lella Natalie N Roberts Rachel R Hartnell Felicity F Bliss Carly C Sierra-Davidson Kailan K Powlson Jonathan J Berrie Eleanor E Tedder Richard R Roman Francois F De Ryck Iris I Nicosia Alfredo A Sullivan Nancy J NJ Stanley Daphne A DA Mbaya Olivier T OT Ledgerwood Julie E JE Schwartz Richard M RM Siani Loredana L Colloca Stefano S Folgori Antonella A Di Marco Stefania S Cortese Riccardo R Wright Edward E Becker Stephan S Graham Barney S BS Koup Richard A RA Levine Myron M MM Volkmann Ariane A Chaplin Paul P Pollard Andrew J AJ Draper Simon J SJ Ballou W Ripley WR Lawrie Alison A Gilbert Sarah C SC Hill Adrian V S AV

The New England journal of medicine 20150128 17

<h4>Background</h4>The West African outbreak of Ebola virus disease that peaked in 2014 has caused more than 11,000 deaths. The development of an effective Ebola vaccine is a priority for control of a future outbreak.<h4>Methods</h4>In this phase 1 study, we administered a single dose of the chimpanzee adenovirus 3 (ChAd3) vaccine encoding the surface glycoprotein of Zaire ebolavirus (ZEBOV) to 60 healthy adult volunteers in Oxford, United Kingdom. The vaccine was administered in three dose leve ...[more]

PMID: 25629663

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Project description:ObjectivesRespiratory syncytial virus (RSV) causes respiratory infection across the world, with infants and the elderly at particular risk of developing severe disease and death. The replication-defective chimpanzee adenovirus (PanAd3-RSV) and modified vaccinia virus Ankara (MVA-RSV) vaccines were shown to be safe and immunogenic in young healthy adults. Here we report an extension to this first-in-man vaccine trial to include healthy older adults aged 60-75 years.MethodsWe evaluated the safety and immunogenicity of a single dose of MVA-RSV given by intra-muscular (IM) injection (n = 6), two doses of IM PanAd3-RSV given 4-weeks apart (n = 6), IM PanAd3-RSV prime and IM MVA-RSV boost 8-weeks later (n = 6), intra-nasal (IN) spray of PanAd3-RSV prime and IM MVA-RSV boost 8-weeks later (n = 6), or no vaccine (n = 6). Safety measures included all adverse events within one week of vaccination and blood monitoring. Immunogenicity measures included serum antibody responses (RSV- and PanAd3-neutralising antibody titres measured by plaque-reduction neutralisation and SEAP assays, respectively), peripheral B-cell immune responses (frequencies of F-specific IgG and IgA antibody secreting cells and memory B-cells by ex vivo and cultured dual-colour ELISpot assays respectively), and peripheral RSV-specific T-cell immune responses (frequencies of IFNγ-producing T-cells by ex vivo ELISpot and CD4+/CD8+/Tfh-like cell frequencies by ICS/FACS assay).ResultsThe vaccines were safe and well tolerated. Compared with each individual baseline immunity the mean fold-changes in serum RSV-neutralising antibody, appearance and magnitude of F-specific IgG and IgA ASCs and expansion of CD4+/CD8+ IFNγ-producing T-cells in peripheral circulation were comparable to the results seen from younger healthy adults who received the same vaccine combination and dose. There were little/no IgA memory B-cell responses in younger and older adults. Expansion of IFNγ-producing T-cells was most marked in older adults following IM prime, with balanced CD4+ and CD8+ T cell responses. The RSV-specific immune responses to vaccination did not appear to be attenuated in the presence of PanAd3 (vector) neutralising antibody.ConclusionsPanAd3-RSV and MVA-RSV was safe and immunogenic in older adults and the parallel induction of RSV-specific humoral and cellular immunity merits further assessment in providing protection from severe disease.

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A Monovalent Chimpanzee Adenovirus Ebola Vaccine Boosted with MVA.

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A Monovalent Chimpanzee Adenovirus Ebola Vaccine Boosted with MVA.

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