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

• Published in: Virology journal 2013-12, Vol.10 (1), p.353-353, Article 353
• Main Authors: Mire, Chad E, Versteeg, Krista M, Cross, Robert W, Agans, Krystle N, Fenton, Karla A, Whitt, Michael A, Geisbert, Thomas W
• Format: Article
• Language: English
• Subjects: Analysis; Animals; Antibodies, Neutralizing - blood; Antibodies, Viral - blood; Antigens; Blood; Chiroptera; Complications and side effects; Disease Models, Animal; distress; Drug Carriers; Female; Ferrets; Genetic aspects; Genetic Vectors; Genomes; glycoproteins; Henipavirus Infections - prevention & control; human diseases; humans; Immunization; Immunoglobulin G; Immunoglobulin G - blood; Membrane proteins; Microbiology; Molecular weight; mortality; Mustela; Nervous system diseases; neutralizing antibodies; Nipah virus; Nipah Virus - genetics; Nipah Virus - immunology; Physiological aspects; Prevention; Proteins; RNA; Severe acute respiratory syndrome; Stomatitis; Studies; Survival Analysis; tissues; vaccination; Vaccination - methods; Vaccines; Vaccines, Synthetic - administration & dosage; Vaccines, Synthetic - genetics; Vaccines, Synthetic - immunology; Vesiculovirus; Vesiculovirus - genetics; viral load; Viral Proteins - genetics; Viral Proteins - immunology; Viral vaccines; Viral Vaccines - administration & dosage; Viral Vaccines - genetics; Viral Vaccines - immunology; Viruses
• ISSN: 1743-422X; 1743-422X
• DOI: 10.1186/1743-422X-10-353

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.