Abstract
Background Questions remain concerning the rapidity of immune responses and the durability and safety of vaccines used to prevent Zaire Ebola virus disease. Methods We conducted two randomized, placebo-controlled trials - one involving adults and one involving children - to evaluate the safety and immune responses of three vaccine regimens against Zaire Ebola virus disease: Ad26.ZEBOV followed by MVA-BN-Filo 56 days later (the Ad26-MVA group), rVSVG-ZEBOV-GP followed by placebo 56 days later (the rVSV group), and rVSVG-ZEBOV-GP followed by rVSVG-ZEBOV-GP 56 days later (the rVSV-booster group). The primary end point was antibody response at 12 months, defined as having both a 12-month antibody concentration of at least 200 enzyme-linked immunosorbent assay units (EU) per milliliter and an increase from baseline in the antibody concentration by at least a factor of 4. Results A total of 1400 adults and 1401 children underwent randomization. Among both adults and children, the incidence of injection-site reactions and symptoms (e.g., feverishness and headache) was higher in the week after receipt of the primary and second or booster vaccinations than after receipt of placebo but not at later time points. These events were largely low-grade. At month 12, a total of 41% of adults (titer, 401 EU per milliliter) and 78% of children (titer, 828 EU per milliliter) had a response in the Ad26-MVA group; 76% (titer, 992 EU per milliliter) and 87% (titer, 1415 EU per milliliter), respectively, had a response in the rVSV group; 81% (titer, 1037 EU per milliliter) and 93% (titer, 1745 EU per milliliter), respectively, had a response in the rVSV-booster group; and 3% (titer, 93 EU per milliliter) and 4% (titer, 67 EU per milliliter), respectively, had a response in the placebo group (P<0.001 for all comparisons of vaccine with placebo). In both adults and children, antibody responses with vaccine differed from those with placebo beginning on day 14. Conclusions No safety concerns were identified in this trial. With all three vaccine regimens, immune responses were seen from day 14 through month 12. (Funded by the National Institutes of Health and others; PREVAC ClinicalTrials.gov number, NCT02876328; EudraCT numbers, 2017-001798-18 and 2017-001798-18/3rd; and Pan African Clinical Trials Registry number, PACTR201712002760250.)
| Original language | English (US) |
|---|---|
| Pages (from-to) | 2411-2424 |
| Number of pages | 14 |
| Journal | New England Journal of Medicine |
| Volume | 387 |
| Issue number | 26 |
| DOIs | |
| State | Published - Dec 29 2022 |
Bibliographical note
Funding Information:Supported in part by the National Institutes of Health , by INSERM , and by the London School of Hygiene and Tropical Medicine. Janssen and Merck Sharp and Dohme provided the vaccines according to the EBOVAC 1 grant agreement. This project is part of the European and Developing Countries Clinical Trials Partnership 2 program supported by the European Union (grant number, RIA2017S-2014–PREVAC-UP). This project received funding from the Innovative Medicines Initiative 2 Joint Undertaking (grant number, 115854), which receives support from the European Union Horizon 2020 Research and Innovation Program and the European Federation of Pharmaceutical Industries and Associations. Funding was provided in part by the National Cancer Institute (grant number, HHSN261201500003I) through the Frederick National Laboratory for Cancer Research and Biomedical Advanced Research and Development Authority (grant number, HHS0100201700012C). The project has been funded by a dedicated INSERM allocation on behalf of the French Research Ministry.
Publisher Copyright:
© 2022 Massachusetts Medical Society.
Keywords
- Global Health
- Infectious Disease
- Infectious Disease General
- Vaccines
- Viral Infections
