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
Author:
Lee Andrew W1, Liu Ken1, Lhomme Edouard2, Blie Julie3, McCullough John4, Onorato Matthew T1, Connor Laurie1, Simon Jakub K1, Dubey Sheri1, VanRheenen Susan1, Deutsch Jonathan1, Owens Abigail1, Morgan Amy1, Welebob Carolee1, Hyatt Donna1, Nair Sunita1, Hamzé Benjamin5, Guindo Oumar6, Sow Samba O7, Beavogui Abdoul H8, Leigh Bailah9, Samai Mohamed9, Akoo Pauline10, Serry-Bangura Alimamy9, Fleck Suzanne10, Secka Fatou10, Lowe Brett10, Watson-Jones Deborah1011, Roy Céline212, Hensley Lisa E13, Kieh Mark3, Coller Beth-Ann G1, Aboulhab Jamila, Aguirre-MacKenzie Michelle, Akoo Pauline, Akpa Esther, Akpata Robert, Albert Sara, Ale Boni Maxime, Alimamy-Bangura Serry, Andong Pierre, Andrews Benetta C, Anoma Stephane, Atri Negin, Augier Augustin, Awuondo Ken, Badio Moses, Bagayoko Aminata, Balde Abby, Balssa Joséphine, Bangura Lamin Molecule, Barrington Kesha, de Saint Fare Eric Barte, Baseler Beth, Bauder Ali, Bauduin Claire, Bawo Luke, Beavogui Abdoul Habib, Belson Michael, Bererd Marion, Beyslow Teedoh, Billioux Jeanne, Billouin-Frazier Shere, Binachon Blandine, Blie Julie, Bockstal Viki, Boison Patricia, Bolay Fatorma, Boly Aliou, Borg Anne-Gaëlle, Bosompem Samuel, Bozman Courtney, Brady Tyler, Browne Sarah, Cagniard Barbara, Cahill Kelly, Cai Yingyun, Camara Aissata Abdoulaye, Camara Aboubacar Keira, Camara Alseny Modet, Campagne Antoine, Campion Cécilia, Cash Jennifer, Chai Siew Pin, Chambelin Francois, Chea Michael, Chêne Geneviève, Chouinard Michelle, Chung Florence, Chung Lucy, Ciancia Séverine, Cisse Papa Ndiaga, Cline-Cole Elfrida, Colin Céline, Coller Beth-Ann, Conde Djélikan Siaka, Cone Katherine, Connor Laurie, Connor Nicholas, Cooper Joseph Boye, Couffin-Cardiergues Sandrine, Coulibaly Fatoumata, Coulibaly Mariam, Crew Page, Dabakuyo-Yonli Sandrine, Dabitao Djeneba, Damerval Thierry, Davis Bionca, Deen Gibrilla Fadlu, Dekeyster Eline, Delfraissy Jean-François, Delmas Christelle, Diakite Mahamadou, Diallo Alpha, Diallo Mamadou Saliou, Diarra Ayouba, Diarra Samba, Diawara Oualy, Dighero-Kemp Bonnie, Diop Samba, Diouf Waly, Dixit Saurabh, Djenabou Barry, Doepel Laurie, D'Ortenzio Eric, Doumbia Seydou, Doumbia Moussa Moise, Douoguih Macaya, Dozier Nelson, Cauwelaert Natasha Dubois, DuChêne Alain, Duvenhage Michael, Eckes Risa, Elliott Elizabeth, Enria Luisa, Espérou Hélène, Etienne Cécile, Eyler Allison, Fakoli Lawrence, Fallah Mosoka, Faye Sylvain, Fayiah John, Fleck Suzanne, Fofana Vemy, Tchos Karine Fouth, Franklin Kokulo, Fusco Daniela, Gaddah Auguste, Gaignet Marylène, Gallagher Katherine, Gichini Harrison, Gozalbes Julia Garcia, Grandits Greg, Gray Maima, Greenwood Brian, Grobler Nico, Gross Robin, Grue Louis, Grund Birgit, Guindo Oumar, Gupta Swati, Haidara Fadima, Hamzé Benjamin, Hancox Emma, Hébert Jean-Christophe, Hendriks Jenny, Hensley Patricia, Hensley Lisa, Higgs Elisabeth, Hilton Trudi, Holley Horace Preston, Hoover Marie, Hughes Melissa, Ilo Dicko, Irvine Skip, Ishola David, Jato Yvonne, Joe Madison, Johnson Melvin, Kaba Aboubacar Sidiki, Kagan Jonathan, Kamara Michael, Kante Myriam, Katoudi Judith, Keita Cheick Mohamed, Keita Sakoba, Keita Seykou, Kennedy Stephen B, Keshinro Babajide, Kiawu Hassan, Kieh Mark, Kirchoff Matthew, Kocher Gregory, Kodio Mamoudou, Kohn Brian, Koivogui Lamine, Kojan Richard, Kolié Cece Francis, Kolié Jacques Seraphin, Kollie David, Kopka Stacy, Koroma Bockarie, Kowuor Dickens, Kpayieli-Freeman Catherine, Kwast Liane, Lacabaratz Christine, Lacarra Boris, Lambert Laurie, Lambeth Courtney, Lancrey-javal Solange, Clifford Lane H, Langba Shadrach, Lawal Bolarinde, Lee Andrew Wen-Tseng, Lee Shona, Lees Shelley, Lefevre Annabelle, Leigh Bailah, Lemarcis Frederic, Lévy Yves, Levy-Marchal Claire, Leyssen Maarten, Lhomme Edouard, Liang Janie, Linga Mameni, Liu Ken, Lowe Brett, Lysander Julia, Mahamadou Ibrah, Mambiah Marvington, Manno Daniela, Marchand Jonathan, Marron Lindsay, Massaquoi Moses B F, Masson Laure, Matard Charly, Mazur Steven, McCullough John, McLean Chelsea, Mercier Noémie, Michavila Pauline, Miller Tracey, Millimouno Niouma Pascal, Miranda Alejandra, Mohamed Soumaya, Mooney Tom, Muamba Dally, Mulbah James, Ndamenyaa Rita Lukoo, Neaton James, Neboua Désiré, Nelson Micki, Newell Kevin, Nguyen Vinh-kim, Njie Yusupha, Njoh Wissedi, Onorato Matthew, Onwuchekwa Uma, Orsega Susan, Ortega-Perez Inmaculada, Osborne Cynthia, Otieno Tuda, Oulaï Davy, Patel Sushma, Peart Danielle, Pettitt James, Peiffer-Smadja Nathan, Phillips Robert, Pierson Jerome, Piot Peter, Piziali Micheal, Pong Stéphany, Postnikova Elena, Proffitt Calvin, Quach Alexandre, Quigley Sinead, Randunu Nadeeka, Richert Laura, Rivière Priscille, Robinson Cynthia, Roy Céline, Russell Amy Falk, Sahr Philip, Samai Mohamed, Samake Sibiry, Sandrus Jen, Sanogo Ibrahim, Sarro Yeya Sadio, Sawadogo Serge, Sayadi Sani, Schvartz Maxime, Schwimmer Christine, Secka Fatou, Sharma Heema, Shelley Denise, Shobayo Bode, Siddiqui Sophia, Simon Jakub, Simpson Shelly, Sivahera Billy Muyisa, Slater Karen, Smolskis Mary, Smout Elizabeth, Snowden Emily, Soutthiphong Anne-Aygline, Sow Amadou, Sow Samba O, Sow Ydrissa, Stirratt Michael, Stoop Jeroen, Subramaniam Guna, Surugue Léa, Swales Nathalie, Tamba Sienneh, Tang Chan, Tangara Cheick, Tapia Milagritos D, Teahton Julius, Tegli Jemee, Termote Monique, Thiebaut Rodolphe, Thompson Greg, Tierney John, Tindanbil Daniel, Touré Abdoulaye, Towalid Elvis, Traina Stacey, Traore Awa, Tyee Tijili, Vallée David, Vatrinet Renaud, Vincent Corine, Vogel Susan, Wallet Cedrick, Warren Travis, Watson-Jones Deborah, Weaver Wade, Wentworth Deborah, Wesseh Cecelia, Whitworth Hilary, Wiedemann Aurelie, Willems Wouter, Wilson Barthalomew, Wolf Jayanthi, Wurie Alie, Yamadjako Delphine, Yaradouno Marcel, Yarmie Quiawiah, Yazdanpanah Yazdan, Yu Shuiqing, Zeggani Zara, Zhou Huanying,
Affiliation:
1. Merck & Co., Inc. , Rahway, New Jersey , USA 2. Inserm, CHU Bordeaux, CIC 1401, EUCLID/F-CRIN Clinical Trials Platform, University of Bordeaux , Bordeaux , France 3. Partnership for Research on Ebola Vaccines in Liberia (PREVAIL) , Monrovia , Liberia 4. Advanced BioMedical Laboratories (ABML) , Cinnaminson, New Jersey , USA {C}%3C!%2D%2D%7C%7CrmComment%7C%7C%3C~show%20%5BAQ%20ID%3DAQ7%20POS%3D28pt%5D~%3E%2D%2D%3E 5. Pôle Recherche Clinique, Institut National de la Santé et de la Recherche Médicale (Inserm) , Paris , France {C}%3C!%2D%2D%7C%7CrmComment%7C%7C%3C~show%20%5BAQ%20ID%3DAQ8%20POS%3D28pt%5D~%3E%2D%2D%3E 6. University Clinical Research Center (UCRC) , Bamako , Mali {C}%3C!%2D%2D%7C%7CrmComment%7C%7C%3C~show%20%5BAQ%20ID%3DAQ9%20POS%3D36pt%5D~%3E%2D%2D%3E 7. CVD-Mali , Bamako , Mali 8. Centre National de Formation et de Recherche en Santé Rurale (CNFRSR) , Maferinyah , Guinea 9. College of Medicine & Allied Health Sciences (COMAHS), University of Sierra Leone , Freetown , Sierra Leone 10. Department of Clinical Research, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine (LSHTM) , London , United Kingdom 11. Mwanza Intervention Trials Unit, National Institute for Medical Research , Mwanza , Tanzania 12. University of Bordeaux, INSERM, MART , UMS 54, F-33000 Bordeaux , France 13. National Bio and Agro-Defense Facility (NBAF), United States Department of Agriculture (USDA) , Manhattan, Kansas , USA
Abstract
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).
Funder
National Institutes of Health (NIH) Institut national de la santé et de la recherche médicale London School of Hygiene and Tropical Medicine Merck Sharp & Dohme LLC Janssen Bavarian Nordic Merck & Co., Inc. Innovative Medicines Initiative 2 Joint Undertaking European Union’s Horizon 2020 research and innovation programme EFPIA US Department of Health and Human Services Administration for Strategic Preparedness & Response Biomedical Advanced Research and Development Authority French Research Ministry
Publisher
Oxford University Press (OUP)
Subject
Infectious Diseases,Microbiology (medical)
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