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

KONSTANTIN V. PUGACHEVAcambis Inc., Cambridge, Massachusetts; Arbovirus Diseases Branch, Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado

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FARSHAD GUIRAKHOOAcambis Inc., Cambridge, Massachusetts; Arbovirus Diseases Branch, Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado

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FRED MITCHELLAcambis Inc., Cambridge, Massachusetts; Arbovirus Diseases Branch, Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado

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SIMEON W. OCRANAcambis Inc., Cambridge, Massachusetts; Arbovirus Diseases Branch, Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado

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MEGAN PARSONSAcambis Inc., Cambridge, Massachusetts; Arbovirus Diseases Branch, Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado

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BARBARA W. JOHNSONAcambis Inc., Cambridge, Massachusetts; Arbovirus Diseases Branch, Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado

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OLGA L. KOSOYAcambis Inc., Cambridge, Massachusetts; Arbovirus Diseases Branch, Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado

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ROBERT S. LANCIOTTIAcambis Inc., Cambridge, Massachusetts; Arbovirus Diseases Branch, Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado

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JOHN T. ROEHRIGAcambis Inc., Cambridge, Massachusetts; Arbovirus Diseases Branch, Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado

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DENNIS W. TRENTAcambis Inc., Cambridge, Massachusetts; Arbovirus Diseases Branch, Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado

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THOMAS P. MONATHAcambis Inc., Cambridge, Massachusetts; Arbovirus Diseases Branch, Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado

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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.

Author Notes

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