Stat1-Deficient Mice Are Not an Appropriate Model for Efficacy Testing of Recombinant Vesicular Stomatitis Virus-Based Filovirus Vaccines.

Abstract

Stat1(-/-) mice lack a response to interferon α, β, and γ, allowing for replication of nonadapted wild-type (wt) Ebolavirus and Marburgvirus. We sought to establish a mouse model for efficacy testing of live attenuated recombinant vesicular stomatitis virus (rVSV)-based filovirus vaccine vectors using wt Ebolavirus and Marburgvirus challenge strains. While infection of immunocompetent mice with different rVSV-based filovirus vectors did not cause disease, infection of Stat1(-/-) mice with the same vectors resulted in systemic infection and lethal outcome for the majority of tested rVSVs. Despite differences in viral loads, organ tropism was remarkably similar between rVSV filovirus vaccine vectors and rVSVwt, with the exception of the brain. In conclusion, Stat1(-/-) mice are not an appropriate immunocompromised mouse model for efficacy testing of live attenuated, replication-competent rVSV vaccine vectors.

• Authors: Andrea Marzi, Lisa Kercher, Joshua Marceau, Anthony York, Julie Callsion, Donald J Gardner, Thomas W Geisbert, Heinz Feldmann
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 212 Suppl 2 Pg. S404-9 (Oct 01 2015) ISSN: 1537-6613 [Electronic] United States
• PMID: 26022440 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
• Copyright: Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Chemical References

• STAT1 Transcription Factor
• Stat1 protein, mouse
• Vaccines, Attenuated
• Viral Vaccines

Topics

• Animals
• Chlorocebus aethiops
• Disease Models, Animal
• Ebolavirus (immunology)
• Filoviridae (immunology)
• Filoviridae Infections (genetics, immunology, virology)
• Genetic Vectors (genetics, immunology)
• Hemorrhagic Fever, Ebola (genetics, immunology, virology)
• Marburg Virus Disease (genetics, immunology, virology)
• Marburgvirus (immunology)
• Mice
• STAT1 Transcription Factor (deficiency, genetics, immunology)
• Vaccines, Attenuated (immunology)
• Vero Cells
• Vesicular Stomatitis (immunology)
• Viral Load (immunology)
• Viral Vaccines (immunology)
• Virus Replication (genetics, immunology)