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. Issue 46 (2nd November 2022)

• Record Type: Journal Article
• Authors: Simon, Jakub K.; Kennedy, Stephen B.; Mahon, Barbara E.; Dubey, Sheri A.; Grant-Klein, Rebecca J.; Liu, Ken; Hartzel, Jonathan; Coller, Beth-Ann G.; Welebob, Carolee; Hanson, Mary E.; Grais, Rebecca F.
• Is Part Of: Vaccine. Volume 40:Issue 46(2022)
• Page Start: 6599
• Page End: 6606
• Publication Date: 2022-11-02
• Subjects: Ebola -- Vaccine -- Immunogenicity; Vaccines -- Periodicals; 615.372
• DOI: 10.1016/j.vaccine.2022.09.037
• Languages: English
• ISSNs: 0264-410X

Abstract

Highlights: In 3 phase 2/3 trials in Africa, vaccination with ERVEBO™ yielded robust immune responses. Baseline seropositive participants had higher binding antibody concentrations postvaccination. There was no association between immune response and age. The immune response was robust & durable regardless of sex, age, or pre-existing antibody level. 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.