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Journal of Virology, August 2006, p. 7929-7938, Vol. 80, No. 16
0022-538X/06/$08.00+0     doi:10.1128/JVI.00263-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

Recombinant Nipah Virus Vaccines Protect Pigs against Challenge

Hana M. Weingartl,^1,2* Yohannes Berhane,¹ Jeff L. Caswell,³ Sheena Loosmore,⁴ Jean-Christophe Audonnet,⁵ James A. Roth,⁶ and Markus Czub^2,7

NCFAD, CFIA, Winnipeg, Canada,¹ NML, PHAC, Winnipeg, Canada,⁷ Department of Medical Microbiology, University of Manitoba, Winnipeg, Canada,² Department of Pathobiology, University of Guelph, Guelph, Canada,³ College of Veterinary Medicine, Iowa State University, Ames, Iowa,⁶ Sanofi Pasteur, Toronto, Canada,⁴ Merial SAS, Lyon, France⁵

Received 6 February 2006/ Accepted 23 May 2006

Nipah virus (NiV), of the family Paramyxoviridae, was isolated in 1999 in Malaysia from a human fatality in an outbreak of severe human encephalitis, when human infections were linked to transmission of the virus from pigs. Consequently, a swine vaccine able to abolish virus shedding is of veterinary and human health interest. Canarypox virus-based vaccine vectors carrying the gene for NiV glycoprotein (ALVAC-G) or the fusion protein (ALVAC-F) were used to intramuscularly immunize four pigs per group, either with 10⁸ PFU each or in combination. Pigs were boosted 14 days postvaccination and challenged with 2.5 x 10⁵ PFU of NiV two weeks later. The combined ALVAC-F/G vaccine induced the highest levels of neutralization antibodies (2,560); despite the low neutralizing antibody levels in the F vaccinees (160), all vaccinated animals appeared to be protected against challenge. Virus was not isolated from the tissues of any of the vaccinated pigs postchallenge, and a real-time reverse transcription (RT)-PCR assay detected only small amounts of viral RNA in several samples. In challenge control pigs, virus was isolated from a number of tissues (10^4.4 PFU/g) or detected by real-time RT-PCR. Vaccination of the ALVAC-F/G vaccinees appeared to stimulate both type 1 and type 2 cytokine responses. Histopathological findings indicated that there was no enhancement of lesions in the vaccinees. No virus shedding was detected in vaccinated animals, in contrast to challenge control pigs, from which virus was isolated from the throat and nose (10^2.9 PFU/ml). Based on the data presented, the combined ALVAC-F/G vaccine appears to be a very promising vaccine candidate for swine.

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* Corresponding author. Mailing address: NCFAD, CFIA, 1015 Arlington St., Winnipeg, Manitoba R3E 3M4, Canada. Phone: (204) 789-2027. Fax: (204) 789-2038. E-mail: hweingartl{at}inspection.gc.ca.

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Journal of Virology, August 2006, p. 7929-7938, Vol. 80, No. 16
0022-538X/06/$08.00+0     doi:10.1128/JVI.00263-06
Copyright © 2006, American Society for Microbiology. All Rights Reserved.

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