A Phase 1 randomized trial of homologous and heterologous filovirus vaccines with a late booster dose

Christina A Rostad; Inci Yildirim; Carol Kao; Jumi Yi; Satoshi Kamidani; Etza Peters; Kathleen Stephens; Theda Gibson; Hui-Mien Hsiao; Karnail Singh; Paul Spearman; Courtney McCracken; Vivien Agbakoba; Kay M Tomashek; Johannes B Goll; Casey E Gelber; Robert A Johnson; Sujin Lee; Kristal Maner-Smith; Steven Bosinger; Eric A Ortlund; Xuemin Chen; Larry J Anderson; Jens Wrammert; Mehul Suthar; Nadine Rouphael; Evan J Anderson

doi:10.1038/s41541-024-01042-4

A Phase 1 randomized trial of homologous and heterologous filovirus vaccines with a late booster dose

NPJ Vaccines. 2024 Dec 23;9(1):255. doi: 10.1038/s41541-024-01042-4.

Authors

Christina A Rostad^{1

2}, Inci Yildirim^{3

4

5

6

7

8}, Carol Kao^{3

4

9}, Jumi Yi^{3

4

10}, Satoshi Kamidani^{3

4}, Etza Peters³, Kathleen Stephens³, Theda Gibson³, Hui-Mien Hsiao³, Karnail Singh^{3

4

11

12}, Paul Spearman^{3

4

11

12}, Courtney McCracken^{4

13}, Vivien Agbakoba¹⁴, Kay M Tomashek¹⁴, Johannes B Goll¹⁵, Casey E Gelber¹⁵, Robert A Johnson^{14

16}, Sujin Lee^{3

17}, Kristal Maner-Smith¹⁸, Steven Bosinger¹⁹, Eric A Ortlund^{19

20}, Xuemin Chen^{3

4}, Larry J Anderson^{3

4}, Jens Wrammert^{3

19}, Mehul Suthar^{3

19}, Nadine Rouphael²¹, Evan J Anderson^{3

4

21

22}

Affiliations

¹ Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA. christina.rostad@emory.edu.
² Center for Childhood Infections and Vaccines, Children's Healthcare of Atlanta, Atlanta, GA, USA. christina.rostad@emory.edu.
³ Department of Pediatrics, Emory University School of Medicine, Atlanta, GA, USA.
⁴ Center for Childhood Infections and Vaccines, Children's Healthcare of Atlanta, Atlanta, GA, USA.
⁵ Department of Pediatrics, Section of Infectious Diseases and Global Health; Yale University School of Medicine, New Haven, CT, USA.
⁶ Department of Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, CT, USA.
⁷ Yale Institute for Global Health, Yale University, New Haven, CT, USA.
⁸ Yale Center for Infection and Immunity, Yale University, New Haven, CT, USA.
⁹ Division of Pediatric Infectious Diseases, Washington University School of Medicine, St Louis, MO, USA.
¹⁰ Merck & Co., Inc., Rahway, NJ, USA.
¹¹ Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
¹² Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
¹³ Center for Research and Evaluation, Kaiser Permanente Georgia, Atlanta, GA, USA.
¹⁴ The Division of Microbiology and Infectious Diseases (DMID), National Institute of Allergy and Infectious Diseases (NIAID), Rockville, MD, USA.
¹⁵ The Emmes Company, LLC, Rockville, MD, USA.
¹⁶ Biomedical Advanced Research and Development Authority (BARDA) Administration for Strategic Preparedness and Response (ASPR), Washington D.C., USA.
¹⁷ Center for ViroScience and Cure, Emory University School of Medicine, Atlanta, GA, USA.
¹⁸ Emory Integrated Metabolomics and Lipidomics Core, Emory University School of Medicine, Atlanta, GA, USA.
¹⁹ Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA, USA.
²⁰ Department of Biochemistry, Emory University School of Medicine, Atlanta, GA, USA.
²¹ Department of Medicine, Emory University School of Medicine, Atlanta, GA, USA.
²² Moderna, Inc, Cambridge, MA, USA.

Abstract

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.

Associated data

ClinicalTrials.gov/NCT02891980

Abstract

Associated data

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