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

Virology Journal

Deborah Middleton³  Christopher C Broder²  Lin-Fa Wang¹  Yan-Ru Feng²  Jean Payne³  John R White³  Fenella Long³  Jessica Haining³  Rachel Arkinstall³  Reuben Klein³  Jackie A Pallister³ 

[1] Program in Emerging Infectious Diseases, Duke-NUS Graduate Medical School, Singapore 169857, Singapore;Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD 20814, USA;CSIRO Biosecurity Flagship, Australian Animal Health Laboratories, 5 Portarlington Road, Geelong, VIC 3220, Australia

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

Others  :  829079
DOI  :  10.1186/1743-422X-10-237

 received in 2013-06-03, accepted in 2013-07-11,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Pallister et al.; licensee BioMed Central Ltd.

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