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A Single-Vector, Single-Injection Trivalent Filovirus Vaccine: Proof of Concept Study in Outbred Guinea Pigs
Chad E Mire1, Joan B Geisbert1, Krista M Versteeg1
1Galveston National Laboratory Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, Texas.
Abstract:
The filoviruses, Marburg marburgvirus (MARV), Zaire ebolavirus (ZEBOV), and Sudan ebolavirus (SEBOV), cause severe and often fatal hemorrhagic fever in humans and nonhuman primates (NHPs). Monovalent recombinant vesicular stomatitis virus (rVSV)-based vaccine vectors, which encode a filovirus glycoprotein (GP) in place of the VSV glycoprotein, have shown 100% efficacy against homologous filovirus challenge in rodent and NHP studies. Here, we examined the utility of a single-vector, single-injection trivalent rVSV vector expressing MARV, ZEBOV, and SEBOV GPs to protect against MARV-, ZEBOV-, and SEBOV-induced disease in outbred Hartley guinea pigs where we observed protection from effects of all 3 filoviruses.
Insights
A novel trivalent vaccine effectively protected guinea pigs against Marburg, Zaire, and Sudan ebolavirus hemorrhagic fevers. This single-vector vaccine shows promise for broad filovirus disease prevention.
Area of Science:
- Virology and Immunology
- Vaccine Development
- Infectious Diseases
Background:
- Filoviruses, including Marburg marburgvirus (MARV), Zaire ebolavirus (ZEBOV), and Sudan ebolavirus (SEBOV), are responsible for severe hemorrhagic fevers in humans and nonhuman primates (NHPs).
- Existing monovalent recombinant vesicular stomatitis virus (rVSV)-based vaccine vectors encoding a single filovirus glycoprotein (GP) have demonstrated high efficacy in preclinical studies.
Purpose of the Study:
- To evaluate the efficacy of a single-vector, trivalent rVSV-based vaccine expressing MARV, ZEBOV, and SEBOV GPs.
- To assess the protective potential of this multivalent vaccine against homologous filovirus-induced disease in a guinea pig model.
Main Methods:
- Development of a single-vector, trivalent rVSV vaccine encoding glycoproteins from MARV, ZEBOV, and SEBOV.
- Administration of a single vaccine dose to outbred Hartley guinea pigs.
- Challenge studies using MARV, ZEBOV, and SEBOV to evaluate protection against disease.
Main Results:
- The trivalent rVSV-based vaccine conferred protection against disease induced by all three filoviruses (MARV, ZEBOV, SEBOV).
- Observed protection in guinea pigs demonstrated the utility of the single-vector, single-injection approach for broad filovirus coverage.
Conclusions:
- A single-vector trivalent rVSV vaccine is a viable strategy for protection against multiple filovirus infections.
- This multivalent vaccine approach offers a promising avenue for developing broad-spectrum filovirus countermeasures.
