A Phase 1 randomized trial of homologous and heterologous filovirus vaccines with a late booster dose
Filoviruses, including Ebola, Marburg, Sudan, and Taï Forest viruses, are zoonotic pathogens that can cause severe viral hemorrhagic fever and death. Developing vaccines that provide durable, broad immunity against multiple filoviruses is a high global health priority. In this Phase 1 trial, we enrolled 60 healthy U.S. adults and evaluated the safety, reactogenicity and immunogenicity of homologous and heterologous MVA-BN®-Filo and Ad26.ZEBOV prime-boost schedules followed in select arms by MVA-BN®-Filo boost at 1 year (NCT02891980). We found that all vaccine regimens had acceptable safety and reactogenicity. The heterologous prime-boost strategy elicited superior Ebola binding and neutralizing antibody, antibody-dependent cellular cytotoxicity (ADCC), and cellular responses compared to homologous prime-boost. The MVA-BN®-Filo boost administered at 1 year resulted in robust humoral and cellular responses that persisted through 6-month follow-up. Overall, our data demonstrated that a heterologous Ad26.ZEBOV/MVA-BN®-Filo prime-boost was safe and immunogenic and established immunologic memory primed to respond after re-exposure. Clinicaltrials.gov, NCT02891980, registered September 1, 2016.
Authors
- Satoshi Kamidani (ORCID: https://orcid.org/0000-0001-6829-0700)
- Courtney McCracken
- Paul W. Spearman (ORCID: https://orcid.org/0000-0001-5393-9511)
- Larry J. Anderson (ORCID: https://orcid.org/0000-0002-0652-6834)
- Mehul S. Suthar (ORCID: https://orcid.org/0000-0002-2686-8380)
- İnci Yıldırım (ORCID: https://orcid.org/0000-0002-8631-0020)
- Nadine Rouphael (ORCID: https://orcid.org/0000-0002-2512-7919)
- Eric A. Ortlund (ORCID: https://orcid.org/0000-0001-8855-3029)
- Carol Kao
- Steven E. Bosinger (ORCID: https://orcid.org/0000-0002-2116-5061)
- Theda Gibson
- Johannes B. Goll (ORCID: https://orcid.org/0000-0002-9968-4080)
- Kristal Maner-Smith (ORCID: https://orcid.org/0000-0002-2274-4284)
- Karnail Singh (ORCID: https://orcid.org/0000-0002-7503-1747)
- Etza Peters
- Christina A. Rostad (ORCID: https://orcid.org/0000-0001-8439-0592)
- Kay M. Tomashek (ORCID: https://orcid.org/0000-0001-7741-7072)
- Evan J. Anderson (ORCID: https://orcid.org/0000-0002-1576-4420)
- Jumi Yi
- Kathleen Stephens
- Vivien Agbakoba
- Sujin Lee (ORCID: https://orcid.org/0000-0002-6692-6880)
- Xuemin Chen
- Jens Wrammert
- Robert A. Johnson
- Casey E. Gelber
- Hui‐Mien Hsiao
Institutions
- Cincinnati Children's Hospital Medical Center (US)
- Merck & Co., Inc., Rahway, NJ, USA (United States) (US)
- Kaiser Permanente (US)
- Emory University (US)
- Washington University in St. Louis (US)
- Biomedical Advanced Research and Development Authority (US)
- Yale University (US)
- Moderna Therapeutics (United States) (US)
- Emmes (United States) (US)
- Yale New Haven Health System (US)
- National Institute of Allergy and Infectious Diseases (US)
- Children's Healthcare of Atlanta (US)
- University of Cincinnati Medical Center (US)
Publication Details
- Journal
- npj Vaccines
- Published
- 2024-12-23
- DOI
- https://doi.org/10.1038/s41541-024-01042-4
- Citations
- 3
- Primary Topic
- Viral Infections and Outbreaks Research
- Type
- article
- Field-Weighted Citation Impact
- 1.17
Funders
- Emory University
- Georgia Research Alliance
- Children's Healthcare of Atlanta
- National Institutes of Health
- School of Medicine, Emory University
- Biomedical Advanced Research and Development Authority
- National Institute of Allergy and Infectious Diseases
- Division of Microbiology and Infectious Diseases, National Institute of Allergy and Infectious Diseases