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Journal of Virology, November 2004, p. 12497-12507, Vol. 78, No. 22
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.22.12497-12507.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

ChimeriVax-West Nile Virus Live-Attenuated Vaccine: Preclinical Evaluation of Safety, Immunogenicity, and Efficacy

Juan Arroyo,1,2 Chuck Miller,1 John Catalan,1 Gwendolyn A. Myers,1 Marion S. Ratterree,3 Dennis W. Trent,1,4 and Thomas P. Monath1*

Acambis, Inc., Cambridge, Massachusetts,1 DynPort Vaccine Co. LLC, Frederick, Maryland,2 Tulane National Primate Research Center, Covington, Louisiana,3 Vaxin, Inc., Birmingham, Alabama4

Received 31 March 2004/ Accepted 9 July 2004

The availability of ChimeriVax vaccine technology for delivery of flavivirus protective antigens at the time West Nile (WN) virus was first detected in North America in 1999 contributed to the rapid development of the vaccine candidate against WN virus described here. ChimeriVax-Japanese encephalitis (JE), the first live- attenuated vaccine developed with this technology has successfully undergone phase I and II clinical trials. The ChimeriVax technology utilizes yellow fever virus (YF) 17D vaccine strain capsid and nonstructural genes to deliver the envelope gene of other flaviviruses as live-attenuated chimeric viruses. Amino acid sequence homology between the envelope protein (E) of JE and WN viruses facilitated targeting attenuating mutation sites to develop the WN vaccine. Here we discuss preclinical studies with the ChimeriVax-WN virus in mice and macaques. ChimeriVax-WN virus vaccine is less neurovirulent than the commercial YF 17D vaccine in mice and nonhuman primates. Attenuation of the virus is determined by the chimeric nature of the construct containing attenuating mutations in the YF 17D virus backbone and three point mutations introduced to alter residues 107, 316, and 440 in the WN virus E protein gene. The safety, immunogenicity, and efficacy of the ChimeriVax-WN02 vaccine in the macaque model indicate the vaccine candidate is expected to be safe and immunogenic for humans.

* Corresponding author. Mailing address: Acambis, Inc., 38 Sidney St., Cambridge, MA 02139. Phone: (617) 761-4200. Fax: (617) 494-1741. E-mail: tom.monath{at}acambis.com.

Journal of Virology, November 2004, p. 12497-12507, Vol. 78, No. 22
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.22.12497-12507.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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