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CONSTRUCTION OF YELLOW FEVER/ST. LOUIS ENCEPHALITIS CHIMERIC VIRUS AND THE USE OF CHIMERAS AS A DIAGNOSTIC TOOL

St. Louis encephalitis (SLE) and West Nile (WN) flaviviruses are genetically closely related and cocirculate in the United States. Virus neutralization tests provide the most specific means for serodiagnosis of infections with these viruses. However, use of wild-type SLE and WN viral strains for laboratory testing is constrained by the biocontainment requirements. We constructed two highly attenuated yellow fever (YF) virus chimeras that contain the premembrane-envelope (prM-E) protein genes from the virulent MSI-7 (isolated in the United States) or the naturally attenuated CorAn9124 (Argentina) SLE strains. The YF/SLE (CorAn version) virus and the previously constructed YF/WN chimera were shown to specifically distinguish between confirmed human SLE and WN cases in a virus neutralization test using patient sera. These chimeras have the potential for use as diagnostic reagents and vaccines against SLE and WN.

Received February 2, 2004. Accepted for publication May 30, 2004.

Acknowledgments: We are grateful to Francis A. Ennis and John Cruz (Center for Infectious Disease and Vaccine Research, University of Massachusetts, Worcester, MA) for providing us access to UMASS BSL-3 facilities for virus and animal experiments and assistance.

Disclosure: Some of the authors of this paper wish to disclose that they are employees of Acambis Inc. and may hold stock in this company. This statement is made in the interest of full disclosure and not because the authors consider this to be a conflict of interest.

Authors’ addresses: Konstantin V. Pugachev, Farshad Guirakhoo, Fred Mitchell, Simeon W. Ocran, Megan Parsons, Dennis W. Trent, and Thomas P. Monath, Acambis Inc., 38 Sidney Street, Cambridge, MA 02139, Telephone: 617-761-4200; Fax: 617-494-1741; E-mails: konstantin.pugachev{at}acambis.com, farshad.guirakhoo{at}acambis.com, fred.mitchell{at}acambis.com, simeon.ocran{at}acambis.com, megan.parsons{at}acambis.com, dennis.trent{at}acambis.com, and tom.monath{at}acambis.com. Barbara W. Johnson, Olga L. Kosoy, Robert S. Lanciotti, and John T. Roehrig, Arbovirus Diseases Branch, Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80522, E-mails: bfj9{at}cdc.gov, oak3{at}cdc.gov, rsl2{at}cdc.gov, and jtr1{at}cdc.gov.

Reprint requests: Konstantin V. Pugachev, Acambis Inc., 38 Sidney Street, Cambridge, MA 02139.

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