A monovalent chimpanzee adenovirus Ebola vaccine boosted with MVA
| Autor: | Katie Ewer, Tommy Rampling, Navin Venkatraman, Georgina Bowyer, Danny Wright, Teresa Lambe, Egeruan B. Imoukhuede, Ruth Payne, Sarah Katharina Fehling, Thomas Strecker, Nadine Biedenkopf, Verena Krähling, Claire M. Tully, Nick J. Edwards., Emma M. Bentley, Dhanraj Samuel, Geneviève Labbé, Jing Jin, Malick Gibani., Alice Minhinnic, Morven Wilkie, Ian Poulton, Natalie Lella, Rachel Roberts, Felicity Hartnell, Carly Bliss, Kailan Sierra-Davidson, Jonathan Powlson, Eleanor Berrie, Richard Tedder, B. Chir., Francois Roman, Iris De Ryck, Alfredo Nicosia, Nancy J. Sullivan, Daphne A. Stanley, Olivier T. Mbaya, Julie E. Ledgerwood, Richard M. Schwartz, Loredana Siani, Stefano Colloca, Antonella Folgori, Stefania Di Marco, Riccardo Cortese, Edward Wright, Stephan Becker, Barney S. Graham, Richard A. Koup, Myron M. Levine, Ariane Volkmann, Paul Chaplin, Andrew J. Pollard, Simon J. Draper, D. Phil., W. Ripley Ballou, Alison Lawrie, Sarah C. Gilbert, and Adrian V. S. Hill |
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| Přispěvatelé: | Ewer, Katie, Rampling, Tommy, Venkatraman, Navin, Bowyer, Georgina, Wright, Danny, Lambe, Teresa, Imoukhuede, Egeruan B., Payne, Ruth, Katharina Fehling, Sarah, Strecker, Thoma, Biedenkopf, Nadine, Krähling, Verena, Tully, Claire M., J. Edwards., Nick, Bentley, Emma M., Samuel, Dhanraj, Labbé, Geneviève, Jin, Jing, Gibani., Malick, Minhinnic, Alice, Wilkie, Morven, Poulton, Ian, Lella, Natalie, Roberts, Rachel, Hartnell, Felicity, Bliss, Carly, Sierra-Davidson, Kailan, Powlson, Jonathan, Berrie, Eleanor, Tedder, Richard, Chir., B., Roman, Francoi, De Ryck, Iri, Nicosia, Alfredo, Sullivan, Nancy J., Stanley, Daphne A., Mbaya, Olivier T., Ledgerwood, Julie E., Schwartz, Richard M., Siani, Loredana, Colloca, Stefano, Folgori, Antonella, Di Marco, Stefania, Cortese, Riccardo, Wright, Edward, Becker, Stephan, Graham, Barney S., Koup, Richard A., Levine, Myron M., Volkmann, Ariane, Chaplin, Paul, Pollard, Andrew J., Draper, Simon J., Phil., D., Ripley Ballou, W., Lawrie, Alison, Gilbert, Sarah C., Hill, and Adrian V. S. |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Zaire ebolavirus Male T-Lymphocytes viruses medicine.disease_cause Antibodies Viral chemistry.chemical_compound 0302 clinical medicine INFECTION Vaccinia 030212 general & internal medicine 11 Medical and Health Sciences B-Lymphocytes Immunity Cellular PROTECTS NONHUMAN-PRIMATES biology ELISPOT General Medicine Middle Aged Ebolavirus 3. Good health VIRUS Cytokines Female Antibody Life Sciences & Biomedicine Adult Pan troglodytes Immunization Secondary IMMUNITY Article 03 medical and health sciences Young Adult Medicine General & Internal Immunity General & Internal Medicine medicine Animals Humans Ebola Vaccines QR355 Ebola virus Science & Technology Ebola vaccine business.industry Hemorrhagic Fever Ebola Virology 030104 developmental biology chemistry Immunology biology.protein Adenoviruses Simian business CHALLENGE |
| ISSN: | 0028-4793 |
| Popis: | BACKGROUND\ud 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.\ud \ud METHODS\ud 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 — 1×1010 viral particles, 2.5×1010 viral particles, and 5×1010 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.\ud \ud RESULTS\ud 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 |
| Databáze: | OpenAIRE |
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