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Open Access Highly Accessed Research

Vaccination of ferrets with a recombinant G glycoprotein subunit vaccine provides protection against Nipah virus disease for over 12 months

Jackie A Pallister12*, Reuben Klein12, Rachel Arkinstall12, Jessica Haining12, Fenella Long12, John R White12, Jean Payne12, Yan-Ru Feng3, Lin-Fa Wang124, Christopher C Broder3 and Deborah Middleton12

Author Affiliations

1 CSIRO Livestock Industries, Australian Animal Health Laboratory, 5 Portarlington Road, Geelong, VIC 3220, Australia

2 CSIRO Biosecurity Flagship, Australian Animal Health Laboratories, 5 Portarlington Road, Geelong, VIC 3220, Australia

3 Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD 20814, USA

4 Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore 169857, Singapore

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Virology Journal 2013, 10:237  doi:10.1186/1743-422X-10-237

Published: 16 July 2013

Abstract

Background

Nipah virus (NiV) is a zoonotic virus belonging to the henipavirus genus in the family Paramyxoviridae. Since NiV was first identified in 1999, outbreaks have continued to occur in humans in Bangladesh and India on an almost annual basis with case fatality rates reported between 40% and 100%.

Methods

Ferrets were vaccinated with 4, 20 or 100 μg HeVsG formulated with the human use approved adjuvant, CpG, in a prime-boost regime. One half of the ferrets were exposed to NiV at 20 days post boost vaccination and the other at 434 days post vaccination. The presence of virus or viral genome was assessed in ferret fluids and tissues using real-time PCR, virus isolation, histopathology, and immunohistochemistry; serology was also carried out. Non-immunised ferrets were also exposed to virus to confirm the pathogenicity of the inoculum.

Results

Ferrets exposed to Nipah virus 20 days post vaccination remained clinically healthy. Virus or viral genome was not detected in any tissues or fluids of the vaccinated ferrets; lesions and antigen were not identified on immunohistological examination of tissues; and there was no increase in antibody titre during the observation period, consistent with failure of virus replication. Of the ferrets challenged 434 days post vaccination, all five remained well throughout the study period; viral genome – but not virus - was recovered from nasal secretions of one ferret given 20 μg HeVsG and bronchial lymph nodes of the other. There was no increase in antibody titre during the observation period, consistent with lack of stimulation of a humoral memory response.

Conclusions

We have previously shown that ferrets vaccinated with 4, 20 or 100 μg HeVsG formulated with CpG adjuvant, which is currently in several human clinical trials, were protected from HeV disease. Here we show, under similar conditions of use, that the vaccine also provides protection against NiV-induced disease. Such protection persists for at least 12 months post-vaccination, with data supporting only localised and self-limiting virus replication in 2 of 5 animals. These results augur well for acceptability of the vaccine to industry.

Keywords:
Nipah virus; Hendra virus; Henipavirus; Paramyxovirus; Ferret; Immunity; Vaccination; Glycoprotein; Subunit vaccine; Longevity