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 BosingerEric A. Ortlund, Xuemin Chen, Larry J. Anderson, Jens Wrammert, Mehul Suthar, Nadine Rouphael, Evan J. Anderson

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number255
Journalnpj Vaccines
Volume9
Issue number1
DOIs
StatePublished - Dec 2024

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