Vesicular stomatitis virus-based vaccines protect nonhuman primates against aerosol challenge with Ebola and Marburg viruses

Abstract

Considerable progress has been made over the last decade in developing candidate preventive vaccines that can protect nonhuman primates against Ebola and Marburg viruses. A vaccine based on recombinant vesicular stomatitis virus (VSV) seems to be particularly robust as it can also confer protection when administered as a postexposure treatment. While filoviruses are not thought to be transmitted by aerosol in nature the inhalation route is among the most likely portals of entry in the setting of a bioterrorist event. At present, all candidate filoviral vaccines have been evaluated against parenteral challenges but none have been tested against an aerosol exposure. Here, we evaluated our recombinant VSV-based Zaire ebolavirus (ZEBOV) and Marburg virus (MARV) vaccines against aerosol challenge in cynomolgus macaques. All monkeys vaccinated with a VSV vector expressing the glycoprotein of ZEBOV were completely protected against an aerosol exposure of ZEBOV. Likewise, all monkeys vaccinated with a VSV vector expressing the glycoprotein of MARV were completely protected against an aerosol exposure of MARV. All control animals challenged by the aerosol route with either ZEBOV or MARV succumbed. Interestingly, disease in control animals appeared to progress slower than previously seen in macaques exposed to comparable doses by intramuscular injection.

Fig. 1

Kaplan–Meier survival curves for cynomolgus macaques vaccinated against ZEBOV or MARV and challenged against ZEBOV (A) or MARV (B).

Fig. 2

(A) Plasma levels of ZEBOV (pfu/ml) from cynomolgus macaques challenged with ZEBOV. (B) Plasma levels of MARV (pfu/ml) from cynomolgus macaques challenged with MARV.

Fig. 3

Circulating levels of IgG against ZEBOV (A) or MARV (B) from cynomolgus macaques challenged with either ZEBOV (A) or MARV (B). (*) Day of filovirus challenge (28 days after single injection vaccination).