Immunogenicity and Vaccine Shedding After 1 or 2 Doses of rVSVΔG-ZEBOV-GP Ebola Vaccine (ERVEBO®): Results From a Phase 2, Randomized, Placebo-controlled Trial in Children and Adults.

Autor:	Lee AW; Merck & Co., Inc., Rahway, New Jersey, USA., Liu K; Merck & Co., Inc., Rahway, New Jersey, USA., Lhomme E; Inserm, CHU Bordeaux, CIC 1401, EUCLID/F-CRIN Clinical Trials Platform, University of Bordeaux, Bordeaux, France., Blie J; Partnership for Research on Ebola Vaccines in Liberia (PREVAIL), Monrovia, Liberia., McCullough J; Advanced BioMedical Laboratories (ABML), Cinnaminson, New Jersey, USA., Onorato MT; Merck & Co., Inc., Rahway, New Jersey, USA., Connor L; Merck & Co., Inc., Rahway, New Jersey, USA., Simon JK; Merck & Co., Inc., Rahway, New Jersey, USA., Dubey S; Merck & Co., Inc., Rahway, New Jersey, USA., VanRheenen S; Merck & Co., Inc., Rahway, New Jersey, USA., Deutsch J; Merck & Co., Inc., Rahway, New Jersey, USA., Owens A; Merck & Co., Inc., Rahway, New Jersey, USA., Morgan A; Merck & Co., Inc., Rahway, New Jersey, USA., Welebob C; Merck & Co., Inc., Rahway, New Jersey, USA., Hyatt D; Merck & Co., Inc., Rahway, New Jersey, USA., Nair S; Merck & Co., Inc., Rahway, New Jersey, USA., Hamzé B; Pôle Recherche Clinique, Institut National de la Santé et de la Recherche Médicale (Inserm), Paris, France., Guindo O; University Clinical Research Center (UCRC), Bamako, Mali., Sow SO; CVD-Mali, Bamako, Mali., Beavogui AH; Centre National de Formation et de Recherche en Santé Rurale (CNFRSR), Maferinyah, Guinea., Leigh B; College of Medicine & Allied Health Sciences (COMAHS), University of Sierra Leone, Freetown, Sierra Leone., Samai M; College of Medicine & Allied Health Sciences (COMAHS), University of Sierra Leone, Freetown, Sierra Leone., Akoo P; Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine (LSHTM), London, United Kingdom., Serry-Bangura A; College of Medicine & Allied Health Sciences (COMAHS), University of Sierra Leone, Freetown, Sierra Leone., Fleck S; Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine (LSHTM), London, United Kingdom., Secka F; Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine (LSHTM), London, United Kingdom., Lowe B; Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine (LSHTM), London, United Kingdom., Watson-Jones D; Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine (LSHTM), London, United Kingdom.; Mwanza Intervention Trials Unit, National Institute for Medical Research, Mwanza, Tanzania., Roy C; Inserm, CHU Bordeaux, CIC 1401, EUCLID/F-CRIN Clinical Trials Platform, University of Bordeaux, Bordeaux, France.; University of Bordeaux, INSERM, MART, UMS 54, F-33000 Bordeaux, France., Hensley LE; National Bio and Agro-Defense Facility (NBAF), United States Department of Agriculture (USDA), Manhattan, Kansas, USA., Kieh M; Partnership for Research on Ebola Vaccines in Liberia (PREVAIL), Monrovia, Liberia., Coller BG; Merck & Co., Inc., Rahway, New Jersey, USA.
Jazyk:	angličtina
Zdroj:	Clinical infectious diseases : an official publication of the Infectious Diseases Society of America [Clin Infect Dis] 2024 Apr 10; Vol. 78 (4), pp. 870-879.
DOI:	10.1093/cid/ciad693
Abstrakt:	Background: The rVSVΔG-ZEBOV-GP vaccine (ERVEBO®) is a single-dose, live-attenuated, recombinant vesicular stomatitis virus vaccine indicated for the prevention of Ebola virus disease (EVD) caused by Zaire ebolavirus in individuals 12 months of age and older. Methods: The Partnership for Research on Ebola VACcination (PREVAC) is a multicenter, phase 2, randomized, double-blind, placebo-controlled trial of 3 vaccine strategies in healthy children (ages 1-17) and adults, with projected 5 years of follow-up (NCT02876328). Using validated assays (GP-ELISA and PRNT), we measured antibody responses after 1-dose rVSVΔG-ZEBOV-GP, 2-dose rVSVΔG-ZEBOV-GP (given on Day 0 and Day 56), or placebo. Furthermore, we quantified vaccine virus shedding in a subset of children's saliva using RT-PCR. Results: In total, 819 children and 783 adults were randomized to receive rVSVΔG-ZEBOV-GP (1 or 2 doses) or placebo. A single dose of rVSVΔG-ZEBOV-GP increased antibody responses by Day 28 that were sustained through Month 12. A second dose of rVSVΔG-ZEBOV-GP given on Day 56 transiently boosted antibody concentrations. In vaccinated children, GP-ELISA titers were superior to placebo and non-inferior to vaccinated adults. Vaccine virus shedding was observed in 31.7% of children, peaking by Day 7, with no shedding observed after Day 28 post-dose 1 or any time post-dose 2. Conclusions: A single dose of rVSVΔG-ZEBOV-GP induced robust antibody responses in children that was non-inferior to the responses induced in vaccinated adults. Vaccine virus shedding in children was time-limited and only observed after the first dose. Overall, these data support the use of rVSVΔG-ZEBOV-GP for the prevention of EVD in at-risk children. Clinical Trials Registration. The study is registered at ClinicalTrials.gov (NCT02876328), the Pan African Clinical Trials Registry (PACTR201712002760250), and the European Clinical Trials Register (EudraCT number: 2017-001798-18). Competing Interests: Potential conflicts of interest. K. L., M. T. O., L. C., S. D., S. V., A. O., C. W., D .H., S. N., and B.-A. C. G. are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ USA, who may own stock and/or hold stock options in Merck & Co., Inc., Rahway, NJ, USA. A. W. L., J. K. S., J. D., and A. M. were employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and may own/have owned stock and/or hold/held stock options in Merck & Co., Inc., Rahway, NJ, USA at the time the study was conducted. E. L., B. H., and C. R. report provision of vaccines from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA to the academic sponsors for the PREVAC trial, but no funding directly to themselves or their institution. J. M. reports provision of sample collection kits for the study sites, provision and support of lab software, technical support and supervision of lab activities, and lab data management. S. O. S. reports payments from Leidos to his institution. P. A. reports support for attending meetings and/or travel including Air tickets and accommodations for attending study related meetings during the conduct of the study. D. W.-J reports funding from Innovative Medicines Initiative 2 Joint Undertaking, additionally D. W.-J. reports funding and donations of an HPV vaccine (Gardasil®) from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA for another unrelated study. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed. (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)
Databáze:	MEDLINE
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