1. A highly attenuated pan-filovirus VesiculoVax vaccine rapidly protects nonhuman primates against Marburg virus and three species of Ebolavirus
- Author
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Courtney Woolsey, Viktoriya Borisevich, Krystle N Agans, Rachel O’Toole, Karla A Fenton, Mack B Harrison, Abhishek N Prasad, Daniel J Deer, Cheryl Gerardi, Nneka Morrison, Robert W Cross, John H Eldridge, Demetrius Matassov, and Thomas W Geisbert
- Subjects
Infectious Diseases ,Immunology and Allergy - Abstract
Background The family Filoviridae consists of several virus members known to cause significant mortality and disease in humans. Among these, Ebola virus (EBOV), Marburg virus (MARV), Sudan virus (SUDV), and Bundibugyo virus (BDBV) are considered the deadliest. The sole US FDA approved filovirus vaccine, Ervebo®, is indicated only for EBOV infections with limited heterologous protection against other filoviruses. In clinical trials, Ervebo® was shown to rapidly protect humans against Ebola disease ten days plus post immunization. Whether multivalent formulations of similar recombinant vesicular stomatitis virus (rVSV)-based vaccines could likewise confer rapid protection is unclear. Methodology/Findings Here, we tested the ability of a highly attenuated, quadrivalent pan-filovirus Vesiculovax vaccine (rVSV-Filo) to elicit fast-acting protection against MARV, EBOV, SUDV, and BDBV. Groups of cynomolgus monkeys were vaccinated seven days before exposure to each of the four viral pathogens. All subjects (100%) immunized one-week prior survived MARV, SUDV, and BDBV challenge; 80% of subjects survived EBOV challenge. Survival correlated with lower viral load, higher glycoprotein-specific IgG titers, and the expression of B cell-, cytotoxic cell-, and antigen presentation-associated transcripts. Conclusions/Significance These results demonstrate multivalent Vesiculovax vaccines are suitable for filovirus outbreak management. The highly attenuated nature of the rVSV-Filo vaccine may be preferable to the Ervebo® “delta G” platform, which induced arthralgia, cutaneous vasculitis, and dermatitis in a subset of recipients.
- Published
- 2023