Recoding structural glycoprotein E2 in classical swine fever virus (CSFV) produces complete virus attenuation in swine and protects infected animals against disease.
Controlling classical swine fever (CSF) mainly involves vaccination with live attenuated vaccines (LAV). Experimental CSFV LAVs has been lately developed through reverse genetics using several different approaches. Here we present that codon de-optimization in the major CSFV structural glycoprotein E2 coding region, causes virus attenuation in swine. Four different mutated constructs (pCSFm1-pCSFm4) were designed using various mutational approaches based on the genetic background of the highly virulent strain Brescia (BICv). Three of these constructs produced infectious viruses (CSFm2v, CSFm3v, and CSFm4v). Animals infected with CSFm2v presented a reduced and extended viremia but did not display any CSF-related clinical signs. Animals that were infected with CSFm2v were protected against challenge with virulent parental BICv. This is the first report describing the development of an attenuated CSFV experimental vaccine by codon usage de-optimization, and one of the few examples of virus attenuation using this methodology that is assessed in a natural host.
Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USA. Electronic address: lauro.velazquez@ars.usda.gov.
Lauro
L
Velazquez-Salinas
Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT 06269, USA. Electronic address: guillermo.risatti@uconn.edu.
Guillermo R
GR
Risatti
Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USA. Electronic address: lauren.holinka@ars.usda.gov.
Lauren G
LG
Holinka
Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USA; Department of Pathobiology and Veterinary Science, University of Connecticut, Storrs, CT 06269, USA. Electronic address: vivian.odonnell@ars.usda.gov.
Vivian
V
O'Donnell
Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USA; Biosecurity Research Institute and Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, KS 66506, USA. Electronic address: jolene.carlson@ars.usda.gov.
Jolene
J
Carlson
Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USA. Electronic address: marialexia.alfano@ars.usda.gov.
Marialexia
M
Alfano
Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USA. Electronic address: luis.rodriguez@ars.usda.gov.
Luis L
LL
Rodriguez
Plum Island Animal Disease Center, DHS, Greenport, NY 11944, USA. Electronic address: consuelo.carrillo@aphis.usda.gov.
Consuelo
C
Carrillo
Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USA. Electronic address: douglas.gladue@ars.usda.gov.
Douglas P
DP
Gladue
Plum Island Animal Disease Center, ARS, USDA, Greenport, NY 11944, USA. Electronic address: manuel.borca@ars.usda.gov.
Manuel V
MV
Borca
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D002478:Cells, Cultured; D006691:Classical Swine Fever / Q000276:immunology / Q000401:mortality / Q000517:prevention & control* / Q000821:virology; D006692:Classical Swine Fever Virus / Q000235:genetics* / Q000276:immunology*; D003062:Codon; D019295:Computational Biology / Q000379:methods; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D009154:Mutation; D013552:Swine; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology*; D014759:Viral Envelope Proteins / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D014765:Viral Vaccines / Q000235:genetics / Q000276:immunology*; D014774:Virulence / Q000235:genetics; D014779:Virus Replication
D003062:Codon; D014613:Vaccines, Attenuated; D014759:Viral Envelope Proteins; D014765:Viral Vaccines; C087086:glycoprotein E2, classical swine fever virus
Classical swine fever virus; Codon de-optimization; Codon usage; Protection; Vaccine development