1. Immunogenicity of rVSVΔG-ZEBOV-GP Ebola vaccine (ERVEBO®) in African clinical trial participants by age, sex, and baseline GP-ELISA titer: A post hoc analysis of three Phase 2/3 trials.
- Author
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Simon JK, Kennedy SB, Mahon BE, Dubey SA, Grant-Klein RJ, Liu K, Hartzel J, Coller BG, Welebob C, Hanson ME, and Grais RF
- Subjects
- Adolescent, Adult, Female, Humans, Male, Middle Aged, Young Adult, Antibodies, Neutralizing, Antibodies, Viral, Enzyme-Linked Immunosorbent Assay, Glycoproteins, Immunogenicity, Vaccine, Immunoglobulin G, Viral Envelope Proteins, Ebola Vaccines, Ebolavirus, Hemorrhagic Fever, Ebola epidemiology
- Abstract
Background: ERVEBO®, a live recombinant vesicular stomatitis virus (VSV) vaccine containing the Zaire ebolavirus glycoprotein (GP) in place of the VSV GP (rVSVΔG-ZEBOV-GP), was advanced through clinical development by Merck & Co., Inc., Rahway, NJ, USA in collaboration with multiple partners to prevent Ebola virus disease (EVD) and has been approved for human use in several countries., Methods: We evaluated data from three Phase 2/3 clinical trials conducted in Liberia (PREVAIL), Guinea (FLW), and Sierra Leone (STRIVE) during the 2013-2016 West African EVD outbreak to assess immune responses using validated assays. We performed a post hoc analysis of the association of vaccine response with sex, age (18-50 yrs & >50 yrs), and baseline (BL) GP-enzyme-linked immunosorbent assay (ELISA) titer (<200 & ≥200 EU/mL), including individual study (PREVAIL, FLW, or STRIVE) data and pooled data from all 3 studies. The endpoints were total IgG antibody response (EU/mL) measured by the GP-ELISA and neutralizing antibody response measured by the plaque reduction neutralization test (PRNT) to rVSVΔG-ZEBOV-GP at Days 28, 180, and 365 postvaccination., Results: In the overall pooled population, in all subgroups, and in each trial independently, GP-ELISA and PRNT geometric mean titers increased from BL, generally peaking at Day 28 and persisting through Day 365. Immune responses were greater in women and participants with BL GP-ELISA ≥ 200 EU/mL, but did not differ across age groups., Conclusion: These data demonstrate that rVSVΔG-ZEBOV-GP elicits a robust and durable immune response through 12 months postvaccination in participants regardless of age, sex, or BL GP-ELISA titer. The higher immune responses observed in women and participants with pre-existing immunity are consistent with those described previously and for other vaccines. Trials were registered as follows: PREVAIL: ClinicalTrials.gov NCT02344407; FLW: Pan African Clinical Trials Registry PACTR201503001057193; STRIVE: ClinicalTrials.gov NCT02378753. Protocols V920-009, 011, and 018., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Declaration of Interest Statement: RFG and BEM have nothing to declare. SBK reports grants/contracts, i.e., Special Projects, from the National Institutes of Health (NIH) as funding source for the conduct of the EVD clinical trial. SAD, RJGK, KL, JH, BAC, CW, MEH, and JKS are (or were) employees of Merck Sharp & Dohme,LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and may own stock or hold stock options in Merck & Co., Inc., Rahway, NJ, USA., (Copyright © 2022 Elsevier Ltd. All rights reserved.)
- Published
- 2022
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