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Open Access Highly Accessed Research

Single injection recombinant vesicular stomatitis virus vaccines protect ferrets against lethal Nipah virus disease

Chad E Mire12, Krista M Versteeg12, Robert W Cross12, Krystle N Agans12, Karla A Fenton12, Michael A Whitt3 and Thomas W Geisbert12*

Author Affiliations

1 Galveston National Laboratory, University of Texas Medical Branch, 301 University Blvd., Galveston, TX, USA

2 Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX, USA

3 Department of Microbiology, Immunology, and Biochemistry, University of Tennessee Health Science Center, 858 Madison Ave., Memphis, TN, USA

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Virology Journal 2013, 10:353  doi:10.1186/1743-422X-10-353

Published: 13 December 2013

Abstract

Background

Nipah virus (NiV) is a highly pathogenic zoonotic agent in the family Paramyxoviridae that is maintained in nature by bats. Outbreaks have occurred in Malaysia, Singapore, India, and Bangladesh and have been associated with 40 to 75% case fatality rates. There are currently no vaccines or postexposure treatments licensed for combating human NiV infection.

Methods and results

Four groups of ferrets received a single vaccination with different recombinant vesicular stomatitis virus vectors expressing: Group 1, control with no glycoprotein; Group 2, the NiV fusion protein (F); Group 3, the NiV attachment protein (G); and Group 4, a combination of the NiV F and G proteins. Animals were challenged intranasally with NiV 28 days after vaccination. Control ferrets in Group 1 showed characteristic clinical signs of NiV disease including respiratory distress, neurological disorders, viral load in blood and tissues, and gross lesions and antigen in target tissues; all animals in this group succumbed to infection by day 8. Importantly, all specifically vaccinated ferrets in Groups 2-4 showed no evidence of clinical illness and survived challenged. All animals in these groups developed anti-NiV F and/or G IgG and neutralizing antibody titers. While NiV RNA was detected in blood at day 6 post challenge in animals from Groups 2-4, the levels were orders of magnitude lower than animals from control Group 1.

Conclusions

These data show protective efficacy against NiV in a relevant model of human infection. Further development of this technology has the potential to yield effective single injection vaccines for NiV infection.

Keywords:
Nipah virus; Henipavirus; Vaccine; Vesicular stomatitis virus; Ferret; Fusion protein; Attachment protein; Glycoprotein; Single-injection; Immunity