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

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

doi:10.1186/1743-422x-10-353

Abstract

BackgroundNipah 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 resultsFour 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.ConclusionsThese 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.

Highlights

Nipah virus (NiV) is a highly pathogenic zoonotic agent in the family Paramyxoviridae that is maintained in nature by bats
Nipah virus (NiV) and Hendra virus (HeV) represent the highly pathogenic zoonotic agents in the paramyxovirus genus Henipavirus with human case fatality rates ranging between 40 and 75% [1]. These viruses are categorized as biosafety level 4 (BSL4) pathogens due to the significant morbidity and mortality associated with disease and the lack of approved vaccines and therapeutics
Recovery of rVSVΔG-NiVB/glycoprotein vectors To investigate the protective efficacy of recombinant vesicular stomatitis virus (rVSV) NiVB vaccine vectors against heterologous NiVM challenge in ferrets, we first developed and recovered two rVSVΔG constructs expressing the NiVB F protein rVSV-ΔG-NiVB/ F-GFP (Figure 1A, blue) or NiVB G protein rVSV-ΔGNiVB/G-GFP (Figure 1A, yellow) using reverse genetics

Summary

Introduction

Nipah virus (NiV) is a highly pathogenic zoonotic agent in the family Paramyxoviridae that is maintained in nature by bats. Nipah virus (NiV) and Hendra virus (HeV) represent the highly pathogenic zoonotic agents in the paramyxovirus genus Henipavirus with human case fatality rates ranging between 40 and 75% [1]. These viruses are categorized as biosafety level 4 (BSL4) pathogens due to the significant morbidity and mortality associated with disease and the lack of approved vaccines and therapeutics. A recombinant subunit vaccine based on the HeV G protein (sGHeV) completely protects small animals against lethal HeV and NiVM infection [10,11,12,13] and more recently was shown to be efficacious in the robust African green monkey model of NiVM infection [14]. The sGHeV vaccine requires a prime-boost strategy to confer protection whereas a single-injection vaccine would be beneficial during outbreaks where there is little time to employ lengthy vaccination regimens

Methods

Results

Conclusion