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Clinical Trial
. 2024 Apr 10;78(4):870-879.
doi: 10.1093/cid/ciad693.

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  1 , Ken Liu  1 , Edouard Lhomme  2 , Julie Blie  3 , John McCullough  4 , Matthew T Onorato  1 , Laurie Connor  1 , Jakub K Simon  1 , Sheri Dubey  1 , Susan VanRheenen  1 , Jonathan Deutsch  1 , Abigail Owens  1 , Amy Morgan  1 , Carolee Welebob  1 , Donna Hyatt  1 , Sunita Nair  1 , Benjamin Hamzé  5 , Oumar Guindo  6 , Samba O Sow  7 , Abdoul H Beavogui  8 , Bailah Leigh  9 , Mohamed Samai  9 , Pauline Akoo  10 , Alimamy Serry-Bangura  9 , Suzanne Fleck  10 , Fatou Secka  10 , Brett Lowe  10 , Deborah Watson-Jones  10   11 , Céline Roy  2   12 , Lisa E Hensley  13 , Mark Kieh  3 , Beth-Ann G Coller  1 ; PREVAC Study Team
Collaborators, Affiliations
Clinical Trial

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 et al. Clin Infect Dis. .

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).

Keywords: Ebola; immunogenicity; pediatrics; vaccine; vaccine shedding.

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Conflict of interest statement

Potential conflicts of interest. K. L., M. T. O., L. C., S. D., S. V., A. O., C. W., D .H., S. N., and B.-A. C. G. are employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ USA, who may own stock and/or hold stock options in Merck & Co., Inc., Rahway, NJ, USA. A. W. L., J. K. S., J. D., and A. M. were employees of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA and may own/have owned stock and/or hold/held stock options in Merck & Co., Inc., Rahway, NJ, USA at the time the study was conducted. E. L., B. H., and C. R. report provision of vaccines from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA to the academic sponsors for the PREVAC trial, but no funding directly to themselves or their institution. J. M. reports provision of sample collection kits for the study sites, provision and support of lab software, technical support and supervision of lab activities, and lab data management. S. O. S. reports payments from Leidos to his institution. P. A. reports support for attending meetings and/or travel including Air tickets and accommodations for attending study related meetings during the conduct of the study. D. W.-J reports funding from Innovative Medicines Initiative 2 Joint Undertaking, additionally D. W.-J. reports funding and donations of an HPV vaccine (Gardasil®) from Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA for another unrelated study. All other authors report no potential conflicts. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

Figures

Figure 1.
Figure 1.
Participant disposition. CONSORT diagram of adults (panel A) and children (panel B) enrolled and randomized to the 1- and 2-dose rVSVΔG-ZEBOV-GP arms and the 1.0-mL placebo arm in the V4.0 PREVAC trial (NCT02876328). Shown here are only the arms analyzed in this report, see primary PREVAC study for the entire CONSORT diagram [12].
Figure 2.
Figure 2.
Pre-specified primary immunogenicity objectives. The bars represent GP-ELISA GMT (EU/mL) with 95% CI for the pooled arm at Day 28 (post-dose 1), and at Month 12 for the 1- and 2-dose arms, compared to placebo. GMTs from children are shown in the solid bars and GMTs from adults are shown in the hatched bars. *Estimated fold difference with 95% CI and results of hypothesis testing (superiority and non-inferiority) are shown above each bar. n = number of participants contributing to the analysis. †Non-inferiority margin =0.5. aPooled = 1- and 2-dose rVSVΔG-ZEBOV-GP arms, post-dose 1. Abbreviations: CI, confidence interval; ELISA, enzyme-linked immunosorbent assay; GMT, geometric mean titer.
Figure 3.
Figure 3.
GP-ELISA antibody responses in adults and children. Binding antibody responses as assessed by GP-ELISA in adults (panels A and B) and children (panels C and D) receiving 1 dose or 2 doses of rVSVΔG-ZEBOV-GP compared to placebo. GMT (EU/mL) and GMFI are displayed with 95% CI. N = GP-ELISA Per-Protocol Population; n = number of participants contributing to the analysis. Abbreviations: CI, confidence interval; ELISA, enzyme-linked immunosorbent assay; GMFI, geometric mean fold increases; GMT, geometric mean titer.
Figure 4.
Figure 4.
PRNT antibody responses in adults and children. Neutralizing antibody responses as assessed by PRNT in adults (panels A and B) and children (panels C and D) receiving 1 or 2 doses of rVSVΔG-ZEBOV-GP compared to placebo. GMT (PRNT60) and GMFI are displayed with 95% CI. N = PRNT Per-Protocol Population; n = number of participants contributing to the analysis. Abbreviations: CI, confidence interval; PRNT, plaque reduction neutralization test; GMFI, geometric mean fold increases; GMT, geometric mean titer.
Figure 5.
Figure 5.
Vaccine virus shedding in a subset of children after the first dose of rVSVΔG-ZEBOV-GP. The percent of children with observed vaccine shedding post the first dose of rVSVΔG-ZEBOV-GP (pooled 1- and 2-dose rVSVΔG-ZEBOV-GP, post-dose 1) compared to placebo with 95% CI. The percentage and the number of children with shedding over the total number of participants contributing to the analysis is displayed above each bar. No shedding was observed post-dose 2 (data not shown). aPooled = 1- and 2-dose rVSVΔG-ZEBOV-GP arms, post-dose 1. Abbreviation: CI, confidence interval.
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References

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