NOTE] Biological and Genetic Properties of SA14-14-2, a Live-Attenuated Japanese Encephalitis Vaccine That Is Currently Available for Humans

Byung-Hak Song; Gil-Nam Yun; Jin-Kyoung Kim; Sang-Im Yun; Young-Min Lee

doi:10.1007/s12275-012-2336-6

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NOTE] Biological and Genetic Properties of SA14-14-2, a Live-Attenuated Japanese Encephalitis Vaccine That Is Currently Available for Humans: Byung-Hak Song ¹, Gil-Nam Yun ¹, Jin-Kyoung Kim ¹, Sang-Im Yun ^1,2, Young-Min Lee ^1,2; Journal of Microbiology 2012;50(4):698-706.
DOI: https://doi.org/10.1007/s12275-012-2336-6
Published online: August 25, 2012

¹Department of Microbiology, College of Medicine, Chungbuk National University, Cheongju 361-763, Republic of Korea, ²Department of Animal, Dairy and Veterinary Sciences, Utah Science Technology and Research (USTAR), College of Agriculture, Utah State University, Logan, UT 84322-4815, United States of America¹Department of Microbiology, College of Medicine, Chungbuk National University, Cheongju 361-763, Republic of Korea, ²Department of Animal, Dairy and Veterinary Sciences, Utah Science Technology and Research (USTAR), College of Agriculture, Utah State University, Logan, UT 84322-4815, United States of America

Corresponding author: Young-Min Lee , Tel: +1-435-797-9667,

Received: 2 July 2012 • Accepted: 13 July 2012

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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 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 plaqueforming 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.

Keywords: Japanese encephalitis virus;SA14-14-2;complete genome;virulence;pathogenesis

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NOTE] Biological and Genetic Properties of SA14-14-2, a Live-Attenuated Japanese Encephalitis Vaccine That Is Currently Available for Humans

J. Microbiol. 2012;50(4):698-706. Published online August 25, 2012

DOI: https://doi.org/10.1007/s12275-012-2336-6

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