Immunogenicity and vaccine shedding after 1 or 2 doses of rVSV¿G-ZEBOV-GP Ebola Vaccine (ERVEBO®): Results from a Phase 2, randomized, placebo-controlled trial in children and adults

Authors: LEE, ANDREW - Merck Research Laboratories; LIU, KEN - Merck Research Laboratories; LHOMME, EDOUARD - Institut National De La Sante Et De La Recherche Medicale (INSERM); BLIE, JULIE - Partnership For Research On Ebola Vaccines In Liberia (PREVAIL); MCCULLOUGH, JOHN - Advanced Biomedical Laboratories (ABML); ONORATO, MATTHEW - Merck Research Laboratories; CONNOR, LAURIE - Merck Research Laboratories; SIMON, JAKUB - Merck Research Laboratories; DUBEY, SHERI - Merck Research Laboratories; VANRHEENE, SUSAN - Merck Research Laboratories; DEUTSCH, JONATHAN - Merck Research Laboratories; OWENS, ABIGAIL - Merck Research Laboratories; MORGAN, AMY - Merck Research Laboratories; WELEBOB, CAROLEE - Merck Research Laboratories; HYATT, DONNA - Merck Research Laboratories; NAIR, SUNITA - Merck Research Laboratories; HAMZE, BENJAMIN - Institut National De La Sante Et De La Recherche Medicale (INSERM); GUINDO, OUMAR - University Clinical Research Center (UCRC); SOW, SAMBA - Center For Vaccine Development-Mali (CVD-MALI); BEAVOGUI, ABDOUL - National Center For Training And Research In Rural Health; LEIGH, BAILAH - University Of Sierra Leone; SAMAI, MOHAMED - University Of Sierra Leone; AKOO, PAULINE - London School Of Hygiene & Tropical Medicine; SERRY-BANGURA, ALIMAMY - University Of Sierra Leone; FLECK, SUZANNE - London School Of Hygiene & Tropical Medicine; SECKA, FATOU - London School Of Hygiene & Tropical Medicine; LOWE, BRETT - London School Of Hygiene & Tropical Medicine; WATSON-JONES, DEBORAH - London School Of Hygiene & Tropical Medicine; ROY, CELINE - Institut National De La Sante Et De La Recherche Medicale (INSERM); Hensley, Lisa; KIEH, MARK - Partnership For Research On Ebola Vaccines In Liberia (PREVAIL); COLLER, BETH-ANN - Merck Research Laboratories

Submitted to: Clinical Infectious Diseases
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/2/2023
Publication Date: 11/15/2023
Citation: Lee, A.W., Liu, K., Lhomme, E., Blie, J., Mccullough, J., Onorato, M.T., Connor, L., Simon, J.K., Dubey, S., Vanrheene, S., Deutsch, J., Owens, A., Morgan, A., Welebob, C., Hyatt, D., Nair, S., Hamze, B., Guindo, O., Sow, S.O., Beavogui, A.H., Leigh, B., Samai, M., Akoo, P., Serry-Bangura, A., Fleck, S., Secka, F., Lowe, B., Watson-Jones, D., Roy, C., Hensley, L.E., Kieh, M., Coller, B.G. 2023. Immunogenicity and vaccine shedding after 1 or 2 doses of rVSV¿G-ZEBOV-GP Ebola Vaccine (ERVEBO®): Results from a Phase 2, randomized, placebo-controlled trial in children and adults. Clinical Infectious Diseases. 78(4):870-879. https://doi.org/10.1093/cid/ciad693.
DOI: https://doi.org/10.1093/cid/ciad693

Interpretive Summary: This paper explored if the Ebola Vaccine was safe and could induce robust and durable immune responses. Previous studies had not explored the safety of the Ebola Vaccine. Ebola virus is spread through bodily fluids. The study found that the immune responses in children was similar to that of adults. Shedding of the vaccine was limited and only seen after the first dose of the vaccine.

Technical Abstract: Background: The rVSV'G-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 rVSV'G-ZEBOV-GP, 2-dose rVSV'G-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 rVSV'G-ZEBOV-GP (1 or 2 doses) or placebo. A single dose of rVSV'G-ZEBOV-GP increased antibody responses by Day 28 that were sustained through Month 12. A second dose of rVSV'G-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 rVSV'G-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 rVSV'G-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).