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Vesicular Stomatitis Virus-Based Vaccines for Prophylaxis and Treatment of Filovirus Infections
Andrea Marzi1, Heinz Feldmann, Thomas W Geisbert
1Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
Abstract:
Ebola and Marburg viruses are emerging/re-emerging zoonotic pathogens that cause severe viral hemorrhagic fever with case-fatality rates up to 90% in humans. Over the last three decades numerous outbreaks, of increasing frequency, have been documented in endemic regions. Furthermore, as a result of increased international travel filovirus infections have been imported into South Africa, Europe and North America. Both viruses possess the potential of being used as bioterrorism agents and are classified as category A pathogens. Currently there is neither a licensed vaccine nor effective treatment available, despite substantial efforts being d́edicated to understanding filovirus well as vaccine and drug development. One of the most promising vaccine platforms is based on replication competent recombinant vesicular stomatitis viruses (rVSV) that express a filovirus glycoprotein as the surface antigen. These rVSVs have been extensively studied in rodent and nonhuman primate models of filovirus disease and, in general, have been shown to be 100% protective in pre-exposure prophylaxis. In addition, rVSVs have demonstrated potential for post-exposure treatment, and thus would be particularly useful in the event of intentional release as well as accidental exposures in outbreak and laboratory settings.
Insights
Ebola and Marburg viruses pose significant public health threats. Recombinant vesicular stomatitis virus (rVSV) vaccines show promise for both pre- and post-exposure protection against filovirus infections.
Area of Science:
- Virology
- Infectious Diseases
- Public Health
Background:
- Ebola and Marburg viruses are zoonotic pathogens causing severe hemorrhagic fever with high fatality rates.
- Outbreaks are increasing in frequency and spreading globally due to international travel.
- These filoviruses are classified as Category A bioterrorism agents, necessitating urgent development of countermeasures.
Purpose of the Study:
- To evaluate the potential of replication competent recombinant vesicular stomatitis viruses (rVSV) as a vaccine platform against filovirus infections.
- To assess the efficacy of rVSV-based vaccines in pre-exposure prophylaxis and post-exposure treatment scenarios.
Main Methods:
- Utilized replication competent recombinant vesicular stomatitis viruses (rVSV) engineered to express filovirus glycoproteins.
- Conducted extensive studies in rodent and nonhuman primate models of filovirus disease.
Main Results:
- rVSV-based vaccines demonstrated 100% protection in pre-exposure prophylaxis models.
- rVSV vaccines also showed potential for post-exposure treatment, offering a critical therapeutic option.
Conclusions:
- Replication competent rVSV expressing filovirus glycoproteins represent a highly promising vaccine platform.
- These rVSV vaccines offer potential for both preventing and treating filovirus infections, crucial for outbreak and accidental exposure settings.
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