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A single-shot ChAd3-MARV vaccine confers rapid and durable protection against Marburg virus in nonhuman primates.

Authors :
Hunegnaw, Ruth
Honko, Anna N.
Wang, Lingshu
Carr, Derick
Murray, Tamar
Shi, Wei
Nguyen, Lam
Storm, Nadia
Dulan, Caitlyn N. M.
Foulds, Kathryn E.
Agans, Krystle N.
Cross, Robert W.
Geisbert, Joan B.
Cheng, Cheng
Ploquin, Aurélie
Stanley, Daphne A.
Geisbert, Thomas W.
Nabel, Gary J.
Sullivan, Nancy J.
Source :
Science Translational Medicine; 12/14/2022, Vol. 14 Issue 675, p1-12, 12p
Publication Year :
2022

Abstract

Marburg virus (MARV) causes a severe hemorrhagic fever disease in primates with mortality rates in humans of up to 90%. MARV has been identified as a category A bioterrorism agent by the Centers for Disease Control and Prevention (CDC) and priority pathogen A by the National Institute of Allergy and Infectious Diseases (NIAID), needing urgent research and development of countermeasures because of the high public health risk it poses. The recent cases of MARV in West Africa underscore the substantial outbreak potential of this virus. The potential for cross-border spread, as had occurred during the 2014–2016 Ebola virus outbreak, illustrates the critical need for MARV vaccines. To support regulatory approval of the chimpanzee adenovirus 3 (ChAd3)–MARV vaccine that has completed phase 1 trials, we showed that the nonreplicating ChAd3 vector, which has a demonstrated safety profile in humans, protected against a uniformly lethal challenge with MARV/Ang. Protective immunity was achieved within 7 days of vaccination and was maintained through 1 year after vaccination. Antigen-specific antibodies were an immune correlate of protection in the acute challenge model, and their concentration was predictive of protection. These results demonstrate that a single-shot ChAd3-MARV vaccine generated a protective immune response that was both rapid and durable with an immune correlate of protection that will support advanced clinical development. Fighting filoviruses: Fighting filovirusesMarburg Virus (MARV) outbreaks remain a major global health concern, and an effective vaccine is urgently needed. Here, Hunegnaw et al. report that a single-shot chimpanzee adenovirus-vectored vaccine expressing the MARV glycoprotein, ChAd3-MARV, confers protection in non-human primates. Animals were protected as soon as one week after vaccination and protection lasted up to a year after vaccination, with antigen-specific antibodies serving as a predictor of protection. Together, these results support clinical use of ChAd3-MARV. -CM [ABSTRACT FROM AUTHOR]

Details

Language :
English
ISSN :
19466234
Volume :
14
Issue :
675
Database :
Complementary Index
Journal :
Science Translational Medicine
Publication Type :
Academic Journal
Accession number :
160783319
Full Text :
https://doi.org/10.1126/scitranslmed.abq6364