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
Andrew W. Lee, Ken Liu, Édouard Lhomme, Julie Blie, John McCullough, Matthew Onorato, Laurie Connor, Jakub K. Simon, Sheri Dubey, Susan M. VanRheenen, Jonathan Deutsch, Abigail Owens, Amy Morgan, Carolee Welebob, Donna Hyatt, Sunita A. Nair, Benjamin Hamzé, Oumar Guindo, Samba O. Sow, Abdoul Habib Béavogui, Bailah Leigh, Mohamed Samai, Pauline Akoo, Alimamy Serry-Bangura, Suzanne Fleck, Fatou Secka, Brett Lowe, Deborah Watson‐Jones, Céline Roy, Lisa E. Hensley, Mark Kieh, Beth-Ann Coller, the PREVAC Study Team, Jamila Aboulhab, Michelle Aguirre-MacKenzie, Pauline Akoo, Esther Akpa, Robert Akpata, Sara Albert, Boni Maxime Ale, Serry Alimamy-Bangura, Pierre Andong, Benetta C. Andrews, Stephane Anoma, Negin Atri, Augustin Augier, Ken Awuondo, Moses Badio, Aminata Bagayoko, Abby Balde, Joséphine Balssa, Lamin Molecule Bangura, Kesha Barrington, Eric Barte de Saint Fare, Beth Baseler, Ali Bauder, Claire Bauduin, Luke Bawo, Abdoul Habib Béavogui, Michael Belson, Marion Bererd, Teedoh Beyslow, Jeanne Billioux, Shere Billouin-Frazier, Blandine Binachon, Julie Blie, Viki Bockstal, Patricia Boison, Fatorma K. Bolay, Aliou Boly, Anne-Gaëlle Borg, Samuel Bosompem, Courtney Bozman, Tyler Brady, Sarah Browne, Barbara Cagniard, Kelly Cahill, Yíngyún Caì, Aissata Abdoulaye Camara, Aboubacar Keira Camara, Alseny Camara, Antoine Campagne, Cécilia Campion, Jennifer Cash, Siew Pin Chai, Francois Chambelin, Michael Chea, Geneviève Chêne, Michelle Chouinard, Florence Chung, Lucy Chung, Séverine Ciancia, Papa Ndiaga Cissé, Elfrida Cline-Cole, Céline Colin, Beth-Ann Coller, Djélikan Siaka Conde, Katherine Cone, Laurie Connor, Nicholas E. Connor
Abstract
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).