npj Vaccines (Mar 2024)
Heterologous cAd3-Ebola and MVA-EbolaZ vaccines are safe and immunogenic in US and Uganda phase 1/1b trials
- Myra Happe,
- Amelia R. Hofstetter,
- Jing Wang,
- Galina V. Yamshchikov,
- LaSonji A. Holman,
- Laura Novik,
- Larisa Strom,
- Francis Kiweewa,
- Salim Wakabi,
- Monica Millard,
- Colleen F. Kelley,
- Sarah Kabbani,
- Srilatha Edupuganti,
- Allison Beck,
- Florence Kaltovich,
- Tamar Murray,
- Susanna Tsukerman,
- Derick Carr,
- Carl Ashman,
- Daphne A. Stanley,
- Aurélie Ploquin,
- Robert T. Bailer,
- Richard Schwartz,
- Fatim Cham,
- Allan Tindikahwa,
- Zonghui Hu,
- Ingelise J. Gordon,
- Nadine Rouphael,
- Katherine V. Houser,
- Emily E. Coates,
- Barney S. Graham,
- Richard A. Koup,
- John R. Mascola,
- Nancy J. Sullivan,
- Merlin L. Robb,
- Julie A. Ake,
- Kirsten E. Lyke,
- Mark J. Mulligan,
- Julie E. Ledgerwood,
- Hannah Kibuuka,
- the VRC 208 and RV 422 study team
Affiliations
- Myra Happe
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Amelia R. Hofstetter
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Jing Wang
- Clinical Monitoring Research Program Directorate, Frederick National Laboratory for Cancer Research
- Galina V. Yamshchikov
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- LaSonji A. Holman
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Laura Novik
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Larisa Strom
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Francis Kiweewa
- Makerere University-Walter Reed Project
- Salim Wakabi
- Makerere University-Walter Reed Project
- Monica Millard
- Walter Reed Army Institute of Research
- Colleen F. Kelley
- Department of Medicine, Division of Infectious Diseases, The Hope Clinic of the Emory Vaccine Center, Emory University
- Sarah Kabbani
- Department of Medicine, Division of Infectious Diseases, The Hope Clinic of the Emory Vaccine Center, Emory University
- Srilatha Edupuganti
- Department of Medicine, Division of Infectious Diseases, The Hope Clinic of the Emory Vaccine Center, Emory University
- Allison Beck
- Department of Medicine, Division of Infectious Diseases, The Hope Clinic of the Emory Vaccine Center, Emory University
- Florence Kaltovich
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Tamar Murray
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Susanna Tsukerman
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Derick Carr
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Carl Ashman
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Daphne A. Stanley
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Aurélie Ploquin
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Robert T. Bailer
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Richard Schwartz
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Fatim Cham
- Makerere University-Walter Reed Project
- Allan Tindikahwa
- Makerere University-Walter Reed Project
- Zonghui Hu
- Biostatistics Research Branch, Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Ingelise J. Gordon
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Nadine Rouphael
- Department of Medicine, Division of Infectious Diseases, The Hope Clinic of the Emory Vaccine Center, Emory University
- Katherine V. Houser
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Emily E. Coates
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Barney S. Graham
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Richard A. Koup
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- John R. Mascola
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Nancy J. Sullivan
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Merlin L. Robb
- Walter Reed Army Institute of Research
- Julie A. Ake
- Walter Reed Army Institute of Research
- Kirsten E. Lyke
- University of Maryland School of Medicine, Center for Vaccine Development and Global Health
- Mark J. Mulligan
- Department of Medicine, Division of Infectious Diseases, The Hope Clinic of the Emory Vaccine Center, Emory University
- Julie E. Ledgerwood
- Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health
- Hannah Kibuuka
- Makerere University-Walter Reed Project
- the VRC 208 and RV 422 study team
- DOI
- https://doi.org/10.1038/s41541-024-00833-z
- Journal volume & issue
-
Vol. 9,
no. 1
pp. 1 – 11
Abstract
Abstract Ebola virus disease (EVD) is a filoviral infection caused by virus species of the Ebolavirus genus including Zaire ebolavirus (EBOV) and Sudan ebolavirus (SUDV). We investigated the safety and immunogenicity of a heterologous prime-boost regimen involving a chimpanzee adenovirus 3 vectored Ebola vaccine [either monovalent (cAd3-EBOZ) or bivalent (cAd3-EBO)] prime followed by a recombinant modified vaccinia virus Ankara EBOV vaccine (MVA-EbolaZ) boost in two phase 1/1b randomized open-label clinical trials in healthy adults in the United States (US) and Uganda (UG). Trial US (NCT02408913) enrolled 140 participants, including 26 EVD vaccine-naïve and 114 cAd3-Ebola-experienced participants (April-November 2015). Trial UG (NCT02354404) enrolled 90 participants, including 60 EVD vaccine-naïve and 30 DNA Ebola vaccine-experienced participants (February-April 2015). All tested vaccines and regimens were safe and well tolerated with no serious adverse events reported related to study products. Solicited local and systemic reactogenicity was mostly mild to moderate in severity. The heterologous prime-boost regimen was immunogenic, including induction of durable antibody responses which peaked as early as two weeks and persisted up to one year after each vaccination. Different prime-boost intervals impacted the magnitude of humoral and cellular immune responses. The results from these studies demonstrate promising implications for use of these vaccines in both prophylactic and outbreak settings.
