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J. Virol. doi:10.1128/JVI.01619-06
Copyright (c) 2006, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

A feline model of acute Nipah virus infection and protection with a soluble glycoprotein-based subunit vaccine

CSIRO Livestock Industries, Australian Animal Health Laboratory, Geelong, Victoria 3220, Australia; Department of Microbiology and Immunology, Uniformed Services University, Bethesda, MD 20814, USA

^* To whom correspondence should be addressed. Email: cbroder{at}usuhs.mil.

	Abstract

Nipah virus (NiV) and Hendra virus (HeV) are paramyxoviruses capable of causing considerable morbidity and mortality in a number of mammalian species including humans. Case reports from outbreaks and previous challenge experiments suggested cats were highly susceptible to NiV infection, responding with a severe respiratory disease and systemic infection. Here we have assessed the cat as a model of experimental NiV infection and use it in the evaluation of a subunit vaccine comprised of soluble G glycoprotein (sG). Two groups of two adult cats each were inoculated subcutaneously with either 500 or 5,000 TCID₅₀ NiV. Animals were monitored closely for disease onset and extensive analysis was conducted on samples and tissues taken during infection and at necropsy to determine viral load and tissue tropism. All animals developed clinical disease 6-9 days post-infection, consistent with previous observations. In a subsequent experiment, two cats were immunized with HeV sG and two with NiV sG. Homologous serum neutralizing titers were greater than 1:20,000 and heterologous titers were greater than 1:20,000 to 16-fold lower. Immunized animals and two additional naïve controls were then challenged subcutaneously with 500 TCID₅₀ NiV. Naïve animals developed clinical disease 6-13 days post-infection, while none of the immunized animals showed any sign of disease. Taqman PCR analysis of samples from naïve animals revealed considerable levels of NiV genome in a wide range of tissues, while genome was evident in only two immunized cats in only four samples, and well below the limit of accurate detection. These results indicate that the cat provides a consistent model for acute NiV infection and associated pathogenesis and an effective subunit vaccine strategy appears achievable.

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