title: Evaluation of a genetically modified foot-and-mouth disease virus vaccine candidate generated by reverse genetics.
abstract: BACKGROUND
  Foot-and-mouth disease (FMD) is the most economically important and highly contagious disease of cloven-hoofed animals worldwide. Control of the disease has been mainly based on large-scale vaccinations with whole-virus inactivated vaccines. In recent years, a series of outbreaks of type O FMD occurred in China (including Chinese Taipei, Chinese Hong Kong) posed a tremendous threat to Chinese animal husbandry. Its causative agent, type O FMDV, has evolved into three topotypes (East-South Asia (ME-SA), Southeast Asia (SEA), Cathay (CHY)) in these regions, which represents an important obstacle to disease control. The available FMD vaccine in China shows generally good protection against ME-SA and SEA topotype viruses infection, but affords insufficient protection against some variants of the CHY topotype. Therefore, the choice of a new vaccine strain is of fundamental importance.
  
  
  RESULTS
  The present study describes the generation of a full-length infectious cDNA clone of FMDV vaccine strain and a genetically modified virus with some amino acid substitutions in antigenic sites 1, 3, and 4, based on the established infectious clone. The recombinant viruses had similar growth properties to the wild O/HN/CHA/93 virus. All swine immunized with inactivated vaccine prepared from the O/HN/CHA/93 were fully protected from challenge with the viruses of ME-SA and SEA topotypes and partially protected against challenge with the virus of CHY topotype at 28 days post-immunization. In contrast, the swine inoculated with the genetically modified vaccine were completely protected from the infection of viruses of the three topotypes.
  
  
  CONCLUSIONS
  Some amino acid substitutions in the FMDV vaccine strain genome did not have an effect on the ability of viral replication in vitro. The vaccine prepared from genetically modified FMDV by reverse genetics significantly improved the protective efficacy to the variant of the CHY topotype, compared with the wild O/HN/CHA/93 virus. Thus, the full-length cDNA clone of FMDV can be a useful tool to develop genetically engineered FMDV vaccine candidates to help control porcinophilic FMD epidemics in China.
authors.affiliation: State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Disease Reference Laboratory, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China.
authors.forename: Pinghua
authors.initials: P
authors.lastname: Li
authors.forename: Xingwen
authors.initials: X
authors.lastname: Bai
authors.forename: Pu
authors.initials: P
authors.lastname: Sun
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.forename: Zengjun
authors.initials: Z
authors.lastname: Lu
authors.forename: Yimei
authors.initials: Y
authors.lastname: Cao
authors.forename: Yuanfang
authors.initials: Y
authors.lastname: Fu
authors.forename: Huifang
authors.initials: H
authors.lastname: Bao
authors.forename: Yingli
authors.initials: Y
authors.lastname: Chen
authors.forename: Baoxia
authors.initials: B
authors.lastname: Xie
authors.forename: Zaixin
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D001483:Base Sequence; D002681:China; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004274:DNA, Recombinant; D004279:DNA, Viral / Q000235:genetics; D004196:Disease Outbreaks / Q000662:veterinary; D005536:Foot-and-Mouth Disease / Q000517:prevention & control*; D029544:Foot-and-Mouth Disease Virus / Q000235:genetics* / Q000276:immunology; D016679:Genome, Viral; D008969:Molecular Sequence Data; D030781:Organisms, Genetically Modified; D059386:Reverse Genetics; D013552:Swine; D013553:Swine Diseases / Q000517:prevention & control*; D014614:Vaccines, Synthetic; D014764:Viral Proteins; D014765:Viral Vaccines / Q000276:immunology*; D014779:Virus Replication
chemical_list: D000956:Antigens, Viral; D018076:DNA, Complementary; D004274:DNA, Recombinant; D004279:DNA, Viral; D014614:Vaccines, Synthetic; D014764:Viral Proteins; D014765:Viral Vaccines