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

Chad E. Mire, Krista M. Versteeg, Robert W. Cross, Krystle N. Agans, Karla A. Fenton, Michael Whitt, Thomas W. Geisbert

Research output: Contribution to journalArticle

30 Citations (Scopus)

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.

Original languageEnglish (US)
Article number353
JournalVirology Journal
Volume10
DOIs
StatePublished - Dec 13 2013

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Nipah Virus
Ferrets
Vesicular Stomatitis
Virus Diseases
Vaccines
Viruses
Injections
Vaccination
Paramyxoviridae
Virus Attachment
Control Groups
Bangladesh
Malaysia
Singapore
Zoonoses
Infection
Neutralizing Antibodies
Nervous System Diseases
Viral Load
GTP-Binding Proteins

All Science Journal Classification (ASJC) codes

  • Virology
  • Infectious Diseases

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Single injection recombinant vesicular stomatitis virus vaccines protect ferrets against lethal Nipah virus disease. / Mire, Chad E.; Versteeg, Krista M.; Cross, Robert W.; Agans, Krystle N.; Fenton, Karla A.; Whitt, Michael; Geisbert, Thomas W.

In: Virology Journal, Vol. 10, 353, 13.12.2013.

Research output: Contribution to journalArticle

Mire, Chad E. ; Versteeg, Krista M. ; Cross, Robert W. ; Agans, Krystle N. ; Fenton, Karla A. ; Whitt, Michael ; Geisbert, Thomas W. / Single injection recombinant vesicular stomatitis virus vaccines protect ferrets against lethal Nipah virus disease. In: Virology Journal. 2013 ; Vol. 10.
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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.",
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