Biological and genetic properties of SA₁₄-14-2, a live-attenuated Japanese encephalitis vaccine that is currently available for humans

• Published in: The journal of microbiology 2012, 50(4), , pp.698-706
• Main Authors: Song, Byung-Hak, Yun, Gil-Nam, Kim, Jin-Kyoung, Yun, Sang-Im, Lee, Young-Min
• Format: Article
• Language: English
• Subjects: 3' Untranslated Regions; amino acid substitution; Animals; antiviral properties; Biomedical and Life Sciences; Cell Line; Cricetinae; Culicidae; death; Disease Models, Animal; encephalitis; Encephalitis Virus, Japanese - genetics; Encephalitis Virus, Japanese - immunology; Encephalitis Virus, Japanese - pathogenicity; Encephalitis, Japanese - pathology; Encephalitis, Japanese - prevention & control; Encephalitis, Japanese - virology; Female; genome; Genome, Viral; hamsters; Humans; insect larvae; Japanese Encephalitis Vaccines - administration & dosage; Japanese Encephalitis Vaccines - genetics; Japanese Encephalitis Vaccines - immunology; Japanese encephalitis virus; kidneys; Life Sciences; live vaccines; Mesocricetus; Mice; Mice, Inbred ICR; microbial growth; Microbiology; Mutagenesis, Insertional; Mutation, Missense; nucleotides; pathogenesis; public health; RNA; RNA, Viral - genetics; Time Factors; vaccination; Vaccines, Attenuated - administration & dosage; Vaccines, Attenuated - genetics; Vaccines, Attenuated - immunology; Viral Plaque Assay; Viral Proteins - genetics; Virulence; virus transmission; viruses; 생물학
• ISSN: 1225-8873; 1976-3794
• DOI: 10.1007/s12275-012-2336-6

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 SA₁₄-14-2, a live-attenuated virus derived from its virulent parent SA₁₄. In this study, we describe the biological properties of SA₁₄-14-2, both in vitro and in vivo, and report the genetic characteristics of its genomic RNA. In BHK-21 (hamster kidney) cells, SA₁₄-14-2 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, SA₁₄-14-2 did not cause any symptoms or death after either intracerebral or peripheral inoculation with a maximum dose of up to 1.5×10³ plaque-forming units (PFU) per mouse. The SA₁₄-14-2 genome consisted of 10977 nucleotides, one nucleotide longer than all the previously reported genomes of SA₁₄-14-2, SA₁₄ and two other SA₁₄-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 SA₁₄-14-2, except for the prM protein-coding region, that differed from SA₁₄ 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.