title: Biological and genetic properties of SA₁₄-14-2, a live-attenuated Japanese encephalitis vaccine that is currently available for humans.
abstract: Japanese encephalitis virus (JEV), a mosquito-borne flavivirus, is a major cause of acute encephalitis, a disease of significance for global public health. In the absence of antiviral therapy to treat JEV infection, vaccination is the most effective method of preventing the disease. In JE-endemic areas, the most widely used vaccine to date is SA(14)-14-2, a live-attenuated virus derived from its virulent parent SA(14). In this study, we describe the biological properties of SA(14)-14-2, both in vitro and in vivo, and report the genetic characteristics of its genomic RNA. In BHK-21 (hamster kidney) cells, SA(14)-14-2 displayed a slight delay in plaque formation and growth kinetics when compared to a virulent JEV strain, CNU/LP2, with no decrease in maximum virus production. The delay in viral growth was also observed in two other cell lines, SH-SY5Y (human neuroblastoma) and C6/36 (mosquito larva), which are potentially relevant to JEV pathogenesis and transmission. In 3-week-old ICR mice, SA(14)-14-2 did not cause any symptoms or death after either intracerebral or peripheral inoculation with a maximum dose of up to 1.5×10(3) plaque-forming units (PFU) per mouse. The SA(14)-14-2 genome consisted of 10977 nucleotides, one nucleotide longer than all the previously reported genomes of SA(14)-14-2, SA(14) and two other SA(14)-derived attenuated viruses. This difference was due to an insertion of one G nucleotide at position 10701 in the 3 noncoding region. Also, we noted a significant number of nucleotide and/or amino acid substitutions throughout the genome of SA(14)-14-2, except for the prM protein-coding region, that differed from SA(14) and/or the other two attenuated viruses. Our results, together with others', provide a foundation not only for the study of JEV virulence but also for the development of new and improved vaccines for JEV.
authors.affiliation: Department of Microbiology, College of Medicine, Chungbuk National University, Cheongju 361-763, Republic of Korea.
authors.forename: Byung-Hak
authors.initials: BH
authors.lastname: Song
authors.forename: Gil-Nam
authors.initials: GN
authors.lastname: Yun
authors.forename: Jin-Kyoung
authors.initials: JK
authors.lastname: Kim
authors.forename: Sang-Im
authors.initials: SI
authors.lastname: Yun
authors.forename: Young-Min
authors.initials: YM
authors.lastname: Lee
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D009033:Culicidae; D004195:Disease Models, Animal; D004664:Encephalitis Virus, Japanese / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D004672:Encephalitis, Japanese / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D005260:Female; D016679:Genome, Viral; D006801:Humans; D022321:Japanese Encephalitis Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D008647:Mesocricetus; D051379:Mice; D008813:Mice, Inbred ICR; D016254:Mutagenesis, Insertional; D020125:Mutation, Missense; D012367:RNA, Viral / Q000235:genetics; D013997:Time Factors; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D010948:Viral Plaque Assay; D014764:Viral Proteins / Q000235:genetics; D014774:Virulence
chemical_list: D020413:3' Untranslated Regions; D022321:Japanese Encephalitis Vaccines; D012367:RNA, Viral; D014613:Vaccines, Attenuated; D014764:Viral Proteins