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Journal articles on the topic 'SA14-14-2 E'

Author: Grafiati

Published: 6 September 2023

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1

Huang, Rong, Shengling Leng, Yalan Feng, Liping Tang, Lei Yuan, and Jian Yang. "Chimeric Japanese Encephalitis Virus SA14/SA14-14-2 Was Virulence Attenuated and Protected the Challenge of Wild-Type Strain SA14." Canadian Journal of Infectious Diseases and Medical Microbiology 2019 (March 3, 2019): 1–7. http://dx.doi.org/10.1155/2019/9179308.

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The attenuated Japanese encephalitis virus (JEV) live vaccine SA14-14-2 prepared from wild-type (WT) strain SA14 was licensed to prevent Japanese encephalitis (JE) in 1989 in China. Many studies showed that the premembrane (prM) and envelope (E) protein were the crucial determinant of virulence and immunogenicity of JEV. So we are interested in whether the substitution of prM/E of JEV WT SA14 with those of vaccine strain SA14-14-2 could decrease neurovirulence and prevent the challenge of JEV WT SA14. Molecular clone technique was used to replace the prM/E gene of JEV WT strain SA14 with those of vaccine strain SA14-14-2 to construct the infectious clone of chimeric virus (designated JEV SA14/SA14-14-2), the chimeric virus recovered from BHK21 cells upon electrotransfection of RNA into BHK21 cells. The results showed that the recovered chimeric virus was highly attenuated in mice, and a single immunization elicited strong protective immunity in a dose-dependent manner. This study increases our understanding of the molecular mechanisms of neurovirulence attenuation and immunogenicity of JEV.

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2

Ye, Qing, Xiao-Feng Li, Hui Zhao, Shi-Hua Li, Yong-Qiang Deng, Rui-Yuan Cao, Ke-Yu Song, et al. "A single nucleotide mutation in NS2A of Japanese encephalitis-live vaccine virus (SA14-14-2) ablates NS1’ formation and contributes to attenuation." Journal of General Virology 93, no. 9 (September 1, 2012): 1959–64. http://dx.doi.org/10.1099/vir.0.043844-0.

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Japanese encephalitis (JE) remains the leading cause of viral encephalitis in the Asia-Pacific region, and the live vaccine SA14-14-2 is currently recommended by WHO and widely used in Asian countries with a good safety and efficacy profile. In this study, we demonstrated that SA14-14-2 failed to produce NS1’, the larger NS1-related protein, compared with its parental strain SA14 in various cells. Sequence analysis and secondary structure prediction identified a single silent mutation G66A in the NS2A-coding region of SA14-14-2 destabilized the conserved pseudoknot structure, which was associated with a −1 ribosomal frame shift event. Using reverse genetic technology and animal study, we provided solid evidence that this single silent mutation G66A in the NS2A gene abolished the production of NS1’ in vitro and reduced neurovirulence and neuroinvasiveness in mice. These findings provide critical information in understanding the molecular mechanism of JE vaccine attenuation and is critical for JE vaccine quality control.

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3

Khou, Cécile, Marco Aurelio Díaz-Salinas, Anaelle da Costa, Christophe Préhaud, Patricia Jeannin, Philippe V. Afonso, Marco Vignuzzi, Monique Lafon, and Nathalie Pardigon. "Comparative analysis of neuroinvasion by Japanese encephalitis virulent and vaccine viral strains in an in vitro model of human blood-brain barrier." PLOS ONE 16, no. 6 (June 4, 2021): e0252595. http://dx.doi.org/10.1371/journal.pone.0252595.

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Japanese encephalitis virus (JEV) is the major cause of viral encephalitis in South East Asia. It has been suggested that, as a consequence of the inflammatory process during JEV infection, there is disruption of the blood-brain barrier (BBB) tight junctions that in turn allows the virus access to the central nervous system (CNS). However, what happens at early times of JEV contact with the BBB is poorly understood. In the present work, we evaluated the ability of both a virulent and a vaccine strain of JEV (JEV RP9 and SA14-14-2, respectively) to cross an in vitro human BBB model. Using this system, we demonstrated that both JEV RP9 and SA14-14-2 are able to cross the BBB without disrupting it at early times post viral addition. Furthermore, we find that almost 10 times more RP9 infectious particles than SA14-14 cross the model BBB, indicating this BBB model discriminates between the virulent RP9 and the vaccine SA14-14-2 strains of JEV. Beyond contributing to the understanding of early events in JEV neuroinvasion, we demonstrate this in vitro BBB model can be used as a system to study the viral determinants of JEV neuroinvasiveness and the molecular mechanisms by which this flavivirus crosses the BBB during early times of neuroinvasion.

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4

Gromowski, Gregory D., Cai-Yen Firestone, and Stephen S. Whitehead. "Genetic Determinants of Japanese Encephalitis Virus Vaccine Strain SA14-14-2 That Govern Attenuation of Virulence in Mice." Journal of Virology 89, no. 12 (April 8, 2015): 6328–37. http://dx.doi.org/10.1128/jvi.00219-15.

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ABSTRACTThe safety and efficacy of the live-attenuated Japanese encephalitis virus (JEV) SA14-14-2 vaccine are attributed to mutations that accumulated in the viral genome during its derivation. However, little is known about the contribution that is made by most of these mutations to virulence attenuation and vaccine immunogenicity. Here, we generated recombinant JEV (rJEV) strains containing JEV SA14-14-2 vaccine-specific mutations that are located in the untranslated regions (UTRs) and seven protein genes or are introduced from PCR-amplified regions of the JEV SA14-14-2 genome. The resulting mutant viruses were evaluated in tissue culture and in mice. The authentic JEV SA14-14-2 (E) protein, with amino acid substitutions L107F, E138K, I176V, T177A, E244G, Q264H, K279M, A315V, S366A, and K439R relative to the wild-type rJEV clone, was essential and sufficient for complete attenuation of neurovirulence. Individually, the nucleotide substitution T39A in the 5′ UTR (5′-UTR-T39A), the capsid (C) protein amino acid substitution L66S (C-L66S), and the complete NS1/2A genome region containing 10 mutations each significantly reduced virus neuroinvasion but not neurovirulence. The levels of peripheral virulence attenuation imposed by the 5′-UTR-T39A and C-L66S mutations, individually, were somewhat mitigated in combination with other vaccine strain-specific mutations, which might be compensatory, and together did not affect immunogenicity. However, a marked reduction in immunogenicity was observed with the addition of the NS1/2A and NS5 vaccine virus genome regions. These results suggest that a second-generation recombinant vaccine can be rationally engineered to maximize levels of immunogenicity without compromising safety.IMPORTANCEThe live-attenuated JEV SA14-14-2 vaccine has been vital for controlling the incidence of disease caused by JEV, particularly in rural areas of Asia where it is endemic. The vaccine was developed >25 years ago by passaging wild-type JEV strain SA14 in tissue cultures and rodents, with intermittent tissue culture plaque purifications, to produce a virus clone that had adequate levels of attenuation and immunogenicity. The vaccine and parent virus sequences were later compared, and mutations were identified throughout the vaccine virus genome, but their contributions to attenuation were never fully elucidated. Here, using reverse genetics, we comprehensively defined the impact of JEV SA14-14-2 mutations on attenuation of virulence and immunogenicity in mice. These results are relevant for quality control of new lots of the current live-attenuated vaccine and provide insight for the rational design of second-generation, live-attenuated, recombinant JEV vaccine candidates.

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5

Li, Guohua, Xianyong Meng, Zhiguang Ren, Entao Li, Feihu Yan, Jing Liu, Ying Zhang, et al. "Characteristics of Chimeric West Nile Virus Based on the Japanese Encephalitis Virus SA14-14-2 Backbone." Viruses 13, no. 7 (June 29, 2021): 1262. http://dx.doi.org/10.3390/v13071262.

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West Nile virus disease (WND) is an arthropod-borne zoonosis responsible for nonspecific fever or severe encephalitis. The pathogen is West Nile virus belonging to the genus Flavivirus, family Flaviviridae. Every year, thousands of cases were reported, which poses significant public health risk. Here, we constructed a West Nile virus chimera, ChiVax-WN01, by replacing the prMΔE gene of JEV SA14-14-2 with that of the West Nile virus NY99. The ChiVax-WN01 chimera showed clear, different characters compared with that of JEV SA14-14-2 and WNV NY99 strain. An animal study indicated that the ChiVax-WN01 chimera presented moderate safety and immunogenicity for 4-week female BALB/c mice.

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6

Liu, Zheng-le, S. Hennessy, B. L. Strom, T. F. Tsai, and S. B. Halstead. "Safety of live-attenuated Japanese encephalitis (JE) vaccine (SA14-14-2)." Journal of Clinical Epidemiology 50 (January 1997): S17. http://dx.doi.org/10.1016/s0895-4356(97)87218-6.

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7

Yang, Dong, Xiao-Feng Li, Qing Ye, Hong-Jiang Wang, Yong-Qiang Deng, Shun-Ya Zhu, Yu Zhang, Shi-Hua Li, and Cheng-Feng Qin. "Characterization of live-attenuated Japanese encephalitis vaccine virus SA14-14-2." Vaccine 32, no. 23 (May 2014): 2675–81. http://dx.doi.org/10.1016/j.vaccine.2014.03.074.

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8

Liu, Xinyu, Xin Zhao, Rui Na, Lili Li, Eberhard Warkentin, Jennifer Witt, Xu Lu, et al. "The structure differences of Japanese encephalitis virus SA14 and SA14-14-2 E proteins elucidate the virulence attenuation mechanism." Protein & Cell 10, no. 2 (May 11, 2018): 149–53. http://dx.doi.org/10.1007/s13238-018-0551-6.

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9

Adetunji, Shakirat A., Dmitriy Smolensky, Dana N. Mitzel, Jeana L. Owens, Carol G. Chitko-McKown, Natalia Cernicchiaro, and Leela E. Noronha. "In Vitro Infection Dynamics of Japanese Encephalitis Virus in Established Porcine Cell Lines." Pathogens 10, no. 11 (November 12, 2021): 1468. http://dx.doi.org/10.3390/pathogens10111468.

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Japanese encephalitis virus (JEV) is a zoonotic mosquito-borne pathogen that regularly causes severe neurological disease in humans in Southeast Asia and the Western Pacific region. Pigs are one of the main amplifying hosts of JEV and play a central role in the virus transmission cycle. The objective of this study was to identify in vitro cell systems to investigate early effects of JEV infection including viral replication and host cell death. Here, we demonstrate the susceptibility of several porcine cell lines to the attenuated genotype III JEV strain SA14-14-2. Monolayers of porcine nasal turbinate (PT-K75), kidney (SK-RST), testis (ST), and monocyte-derived macrophage (CΔ2+) cells were infected with SA14-14-2 for up to five days at a multiplicity of infection (MOI) of 0.1. The hamster kidney cell line BHK-21, previously shown to be susceptible to SA14-14-2, was used as a positive control. Culture supernatants and cells were collected between 0 and 120 h post infection (hpi), and monolayers were observed for cytopathic effect (CPE) using brightfield microscopy. The number of infectious virus particles was quantified by plaque assay and cell viability was determined using trypan blue staining. An indirect immunofluorescence assay was used to detect the presence of JEV NS1 antigens in cells infected at 1 MOI. All four porcine cell lines demonstrated susceptibility to SA14-14-2 and produced infectious virus by 12 hpi. Virus titers peaked at 48 hpi in CΔ2+, BHK-21, and SK-RST cells, at 72 hpi in PT-K75, and at 120 hpi in ST cells. CPE was visible in infected CΔ2+ and BHK-21 cells, but not the other three cell lines. The proportion of viable cells, as measured by trypan blue exclusion, declined after 24 hpi in BHK-21 and 48 hpi in CΔ2+ cells, but did not substantially decline in SK-RST, PT-K75 or ST cells. At 48 hpi, JEV NS1 was detected in all infected cell lines by fluorescence microscopy. These findings demonstrate several porcine cell lines which have the potential to serve as useful research tools for investigating JEV infection dynamics and host cell mechanisms in a natural amplifying host species, such as pigs, in vitro.

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10

Arroyo, Juan, Farshad Guirakhoo, Sabine Fenner, Zhen-Xi Zhang, Thomas P. Monath, and Thomas J. Chambers. "Molecular Basis for Attenuation of Neurovirulence of a Yellow Fever Virus/Japanese Encephalitis Virus Chimera Vaccine (ChimeriVax-JE)." Journal of Virology 75, no. 2 (January 15, 2001): 934–42. http://dx.doi.org/10.1128/jvi.75.2.934-942.2001.

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ABSTRACT A yellow fever virus (YFV)/Japanese encephalitis virus (JEV) chimera in which the structural proteins prM and E of YFV 17D are replaced with those of the JEV SA14-14-2 vaccine strain is under evaluation as a candidate vaccine against Japanese encephalitis. The chimera (YFV/JEV SA14-14-2, or ChimeriVax-JE) is less neurovirulent than is YFV 17D vaccine in mouse and nonhuman primate models (F. Guirakhoo et al., Virology 257:363–372, 1999; T. P. Monath et al., Vaccine 17:1869–1882, 1999). Attenuation depends on the presence of the JEV SA14-14-2 E protein, as shown by the high neurovirulence of an analogous YFV/JEV Nakayama chimera derived from the wild JEV Nakayama strain (T. J. Chambers, A. Nestorowicz, P. W. Mason, and C. M. Rice, J. Virol. 73:3095–3101, 1999). Ten amino acid differences exist between the E proteins of ChimeriVax-JE and the YFV/JEV Nakayama virus, four of which are predicted to be neurovirulence determinants based on various sequence comparisons. To identify residues that are involved in attenuation, a series of intratypic YFV/JEV chimeras containing either single or multiple amino acid substitutions were engineered and tested for mouse neurovirulence. Reversions in at least three distinct clusters were required to restore the neurovirulence typical of the YFV/JEV Nakayama virus. Different combinations of cluster-specific reversions could confer neurovirulence; however, residue 138 of the E protein (E138) exhibited a dominant effect. No single amino acid reversion produced a phenotype significantly different from that of the ChimeriVax-JE parent. Together with the known genetic stability of the virus during prolonged cell culture and mouse brain passage, these findings support the candidacy of this experimental vaccine as a novel live-attenuated viral vaccine against Japanese encephalitis.

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11

Xin, Yu Yong, Ao Jian, Guo Yu Peng, Li Ho Min, and Zhang Guo Ming. "Safety of a Live-Attenuated Japanese Encephalitis Virus Vaccine (SA14-14-2) for Children." American Journal of Tropical Medicine and Hygiene 39, no. 2 (August 1, 1988): 214–17. http://dx.doi.org/10.4269/ajtmh.1988.39.214.

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12

Hennessy, S., B. L. Strom, W. B. Bilker, L. Zhengle, W. Chao-Min, L. Hui-Lian, W. Tai-Xiang, et al. "Effectiveness of live-attenuated Japanese encephalitis vaccine (SA14-14-2): a case-control study." Lancet 347, no. 9015 (June 1996): 1583–86. http://dx.doi.org/10.1016/s0140-6736(96)91075-2.

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13

Li, Guohua, Hongli Jin, Xin Nie, Yongkun Zhao, Na Feng, Zongxi Cao, Shuyi Tan, et al. "Development of a reverse genetics system for Japanese encephalitis virus strain SA14-14-2." Virus Genes 55, no. 4 (June 3, 2019): 550–56. http://dx.doi.org/10.1007/s11262-019-01674-y.

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14

Li, Xiao-Feng, Wei Zhao, Fang Lin, Qing Ye, Hong-Jiang Wang, Dong Yang, Shi-Hua Li, et al. "Development of chimaeric West Nile virus attenuated vaccine candidate based on the Japanese encephalitis vaccine strain SA14-14-2." Journal of General Virology 94, no. 12 (December 1, 2013): 2700–2709. http://dx.doi.org/10.1099/vir.0.059436-0.

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Mosquito-borne flaviviruses include a large group of important human medical pathogens. Several chimaeric flaviviruses have been constructed, and show potential for vaccine development. Although Japanese encephalitis virus (JEV) live vaccine SA14-14-2 has been widely used with ideal safety and efficacy profiles, no chimaeric flavivirus based on the JEV vaccine has been described to date. Based on the reverse genetic system of the JEV vaccine SA14-14-2, a novel live chimaeric flavivirus carrying the protective antigens of West Nile virus (WNV) was constructed and recovered in this study. The resulting chimaera (ChinWNV) replicated efficiently in both mammalian and mosquito cells and possessed genetic stability after in vitro serial passaging. ChinWNV exhibited a small-plaque phenotype, and its replication was significantly restricted in mouse peripheral blood and brain compared with parental WNV. Importantly, ChinWNV was highly attenuated with regard to both neurovirulence and neuroinvasiveness in mice. Furthermore, a single ChinWNV immunization stimulated robust WNV-specific adaptive immune responses in mice, conferring significant protection against lethal WNV infection. Our results demonstrate that chimaeric flaviviruses based on the JEV vaccine can serve as a powerful platform for vaccine development, and that ChinWNV represents a potential WNV vaccine candidate that merits further development.

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15

Sohn, Young Mo, Min Soo Park, Hye Ok Rho, Laura J. Chandler, Robert E. Shope, and Theodore F. Tsai. "Primary and booster immune responses to SA14-14-2 Japanese encephalitis vaccine in Korean infants." Vaccine 17, no. 18 (May 1999): 2259–64. http://dx.doi.org/10.1016/s0264-410x(99)00006-7.

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16

Liu, Xinyu, Danhua Zhao, Lili Jia, Hongshan Xu, Rui Na, Yonghong Ge, Shaoxiang Liu, Yongxin Yu, and Yuhua Li. "Genetic and neuroattenuation phenotypic characteristics and their stabilities of SA14-14-2 vaccine seed virus." Vaccine 36, no. 31 (July 2018): 4650–56. http://dx.doi.org/10.1016/j.vaccine.2018.06.040.

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17

Hong, Sun Pyo, Wang-Don Yoo, Robert Putnak, Kenneth H. Eckels, Hyune Mo Rho, and Soo-Ok Kim. "Nucleotide Sequence of Envelope Protein of Japanese Encephalitis Virus SA14-14-2 Adapted to Vero Cells." DNA Sequence 12, no. 5-6 (January 2001): 437–42. http://dx.doi.org/10.3109/10425170109084471.

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18

Li, Shi-Hua, Xiao-Feng Li, Hui Zhao, Yong-Qiang Deng, Xue-Dong Yu, Shun-Ya Zhu, Tao Jiang, Qing Ye, E.-De Qin, and Cheng-Feng Qin. "Development and characterization of the replicon system of Japanese encephalitis live vaccine virus SA14-14-2." Virology Journal 10, no. 1 (2013): 64. http://dx.doi.org/10.1186/1743-422x-10-64.

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19

Chambers, Thomas J., Ann Nestorowicz, Peter W. Mason, and Charles M. Rice. "Yellow Fever/Japanese Encephalitis Chimeric Viruses: Construction and Biological Properties." Journal of Virology 73, no. 4 (April 1, 1999): 3095–101. http://dx.doi.org/10.1128/jvi.73.4.3095-3101.1999.

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ABSTRACT A system has been developed for generating chimeric yellow fever/Japanese encephalitis (YF/JE) viruses from cDNA templates encoding the structural proteins prM and E of JE virus within the backbone of a molecular clone of the YF17D strain. Chimeric viruses incorporating the proteins of two JE strains, SA14-14-2 (human vaccine strain) and JE Nakayama (JE-N [virulent mouse brain-passaged strain]), were studied in cell culture and laboratory mice. The JE envelope protein (E) retained antigenic and biological properties when expressed with its prM protein together with the YF capsid; however, viable chimeric viruses incorporating the entire JE structural region (C-prM-E) could not be obtained. YF/JE(prM-E) chimeric viruses grew efficiently in cells of vertebrate or mosquito origin compared to the parental viruses. The YF/JE SA14-14-2 virus was unable to kill young adult mice by intracerebral challenge, even at doses of 106 PFU. In contrast, the YF/JE-N virus was neurovirulent, but the phenotype resembled parental YF virus rather than JE-N. Ten predicted amino acid differences distinguish the JE E proteins of the two chimeric viruses, therefore implicating one or more residues as virus-specific determinants of mouse neurovirulence in this chimeric system. This study indicates the feasibility of expressing protective antigens of JE virus in the context of a live, attenuated flavivirus vaccine strain (YF17D) and also establishes a genetic system for investigating the molecular basis for neurovirulence determinants encoded within the JE E protein.

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20

Erra, Elina O., and Anu Kantele. "The Vero cell-derived, inactivated, SA14-14-2 strain-based vaccine (Ixiaro) for prevention of Japanese encephalitis." Expert Review of Vaccines 14, no. 9 (July 10, 2015): 1167–79. http://dx.doi.org/10.1586/14760584.2015.1061939.

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21

Sohn, Young Mo. "Primary and Booster Immune Responses to Live Attenuated SA14-14-2 Japanease Encephalitis Vaccine in Korean Infants." Korean Journal of Pediatric Infectious Diseases 5, no. 1 (1998): 67. http://dx.doi.org/10.14776/kjpid.1998.5.1.67.

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22

Yu, Yongxin. "Phenotypic and genotypic characteristics of Japanese encephalitis attenuated live vaccine virus SA14-14-2 and their stabilities." Vaccine 28, no. 21 (May 2010): 3635–41. http://dx.doi.org/10.1016/j.vaccine.2010.02.105.

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23

Yun, Sang-Im, Byung-Hak Song, Irina A. Polejaeva, Christopher J. Davies, Kenneth L. White, and Young-Min Lee. "Comparison of the live-attenuated Japanese encephalitis vaccine SA14 -14-2 strain with its pre-attenuated virulent parent SA14 strain: similarities and differences in vitro and in vivo." Journal of General Virology 97, no. 10 (October 13, 2016): 2575–91. http://dx.doi.org/10.1099/jgv.0.000574.

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24

Wang, Ran, Meng Zhang, Linlin Zhang, Mengjia Liu, Chao Shan, Jing An, and Zhengde Xie. "Japanese Encephalitis Vaccine Generates Cross-Reactive Memory T Cell Responses to Zika Virus in Humans." Journal of Tropical Medicine 2022 (November 19, 2022): 1–10. http://dx.doi.org/10.1155/2022/8379286.

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Objective. Zika virus (ZIKV) and Japanese encephalitis virus (JEV) are mosquito-borne flaviviruses with sequence homology. ZIKV circulates in some regions where JEV also circulates, or where JE vaccination is used. Cross-immunity between flaviviruses exists, but the precise mechanisms remain unclear. We previously demonstrated that T cell immunity induced by the live-attenuated Japanese encephalitis (JE) SA14-14-2 vaccine conferred protective immunity against ZIKV infection in mice, which could even bypass antibody-dependent enhancement. However, the role of T cell immune, especially memory T cell subsets, in cross-reactive immune responses between JE vaccine and ZIKV in humans has not been reported. Methods. We examined central and effector memory CD4+ and CD8+ T cell (TCM and TEM) responses (including degranulation, cytokines, and chemokines) in the presence of JEV and ZIKV, respectively, by using qualified peripheral blood mononuclear cell samples from 18 children who had recently received a two-dose course of JE vaccine SA14-14-2 as well as seven children without JE vaccination. Results. Cross-reactive CD8+ TCM in response to ZIKV was characterized by secretion of IFN-γ, whereas CD8+ TEM did not show significant upregulation of functional factors. In the presence of ZIKV, IFN-γ and TNF-α expression was upregulated by CD4+ TEM, and the expression signature of CD4+ TCM is more cytotoxic potential. Conclusions. We profiled the cross-reactive memory T cell responses to ZIKV in JE vaccine recipients. These data will provide evidence for the mechanism of cross-reactive memory T cell immune responses between JEV and ZIKV and a more refined view of bivalent vaccine design strategy.

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Monath, T. P., I. Levenbook, K. Soike, Z. X. Zhang, M. Ratterree, K. Draper, A. D. T. Barrett, et al. "Chimeric Yellow Fever Virus 17D-Japanese Encephalitis Virus Vaccine: Dose-Response Effectiveness and Extended Safety Testing in Rhesus Monkeys." Journal of Virology 74, no. 4 (February 15, 2000): 1742–51. http://dx.doi.org/10.1128/jvi.74.4.1742-1751.2000.

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ABSTRACT ChimeriVax-JE is a live, attenuated recombinant virus prepared by replacing the genes encoding two structural proteins (prM and E) of yellow fever 17D virus with the corresponding genes of an attenuated strain of Japanese encephalitis virus (JE), SA14-14-2 (T. J. Chambers et al., J. Virol. 73:3095–3101, 1999). Since the prM and E proteins contain antigens conferring protective humoral and cellular immunity, the immune response to vaccination is directed principally at JE. The prM-E genome sequence of the ChimeriVax-JE in diploid fetal rhesus lung cells (FRhL, a substrate acceptable for human vaccines) was identical to that of JE SA14-14-2 vaccine and differed from sequences of virulent wild-type strains (SA14 and Nakayama) at six amino acid residues in the envelope gene (E107, E138, E176, E279, E315, and E439). ChimeriVax-JE was fully attenuated for weaned mice inoculated by the intracerebral (i.c.) route, whereas commercial yellow fever 17D vaccine (YF-Vax) caused lethal encephalitis with a 50% lethal dose of 1.67 log10 PFU. Groups of four rhesus monkeys were inoculated by the subcutaneous route with 2.0, 3.0, 4.0, and 5.0 log10PFU of ChimeriVax-JE. All 16 monkeys developed low viremias (mean peak viremia, 1.7 to 2.1 log10 PFU/ml; mean duration, 1.8 to 2.3 days). Neutralizing antibodies appeared between days 6 and 10; by day 30, neutralizing antibody responses were similar across dose groups. Neutralizing antibody titers to the homologous (vaccine) strain were higher than to the heterologous wild-type JE strains. All immunized monkeys and sham-immunized controls were challenged i.c. on day 54 with 5.2 log10 PFU of wild-type JE. None of the immunized monkeys developed viremia or illness and had mild residual brain lesions, whereas controls developed viremia, clinical encephalitis, and severe histopathologic lesions. Immunized monkeys developed significant (≥4-fold) increases in serum and cerebrospinal fluid neutralizing antibodies after i.c. challenge. In a standardized test for neurovirulence, ChimeriVax-JE and YF-Vax were compared in groups of 10 monkeys inoculated i.c. and analyzed histopathologically on day 30. Lesion scores in brains and spinal cord were significantly higher for monkeys inoculated with YF-Vax. ChimeriVax-JE meets preclinical safety and efficacy requirements for a human vaccine; it appears safer than yellow fever 17D vaccine but has a similar profile of immunogenicity and protective efficacy.

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26

Monath, Thomas P., Juan Arroyo, Inessa Levenbook, Zhen-Xi Zhang, John Catalan, Ken Draper, and Farshad Guirakhoo. "Single Mutation in the Flavivirus Envelope Protein Hinge Region Increases Neurovirulence for Mice and Monkeys but Decreases Viscerotropism for Monkeys: Relevance to Development and Safety Testing of Live, Attenuated Vaccines." Journal of Virology 76, no. 4 (February 15, 2002): 1932–43. http://dx.doi.org/10.1128/jvi.76.4.1932-1943.2002.

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ABSTRACT A chimeric yellow fever (YF) virus/Japanese encephalitis (JE) virus vaccine (ChimeriVax-JE) was constructed by insertion of the prM-E genes from the attenuated JE virus SA14-14-2 vaccine strain into a full-length cDNA clone of YF 17D virus. Passage in fetal rhesus lung (FRhL) cells led to the emergence of a small-plaque virus containing a single Met→Lys amino acid mutation at E279, reverting this residue from the SA14-14-2 to the wild-type amino acid. A similar virus was also constructed by site-directed mutagenesis (J. Arroyo, F. Guirakhoo, S. Fenner, Z.-X. Zhang, T. P. Monath, and T. J. Chambers, J. Virol. 75:934-942, 2001). The E279 mutation is located in a beta-sheet in the hinge region of the E protein that is responsible for a pH-dependent conformational change during virus penetration from the endosome into the cytoplasm of the infected cell. In independent transfection-passage studies with FRhL or Vero cells, mutations appeared most frequently in hinge 4 (bounded by amino acids E266 to E284), reflecting genomic instability in this functionally important region. The E279 reversion caused a significant increase in neurovirulence as determined by the 50% lethal dose and survival distribution in suckling mice and by histopathology in rhesus monkeys. Based on sensitivity and comparability of results with those for monkeys, the suckling mouse is an appropriate host for safety testing of flavivirus vaccine candidates for neurotropism. After intracerebral inoculation, the E279 Lys virus was restricted with respect to extraneural replication in monkeys, as viremia and antibody levels (markers of viscerotropism) were significantly reduced compared to those for the E279 Met virus. These results are consistent with the observation that empirically derived vaccines developed by mouse brain passage of dengue and YF viruses have increased neurovirulence for mice but reduced viscerotropism for humans.

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27

Yang, Jian, Huiqiang Yang, Zhushi Li, Wei Wang, Hua Lin, Lina Liu, Qianzhi Ni, et al. "Envelope Protein Mutations L107F and E138K Are Important for Neurovirulence Attenuation for Japanese Encephalitis Virus SA14-14-2 Strain." Viruses 9, no. 1 (January 21, 2017): 20. http://dx.doi.org/10.3390/v9010020.

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Tsai, T. F., Yu Yong‐Xin, Jia Li Li, Ravithat Putvatana, Zhang Ran, Wang Shougui, and Scott B. Halstead. "Immunogenicity of Live Attenuated SA14–14–2 Japanese Encephalitis Vaccine—A Comparison of 1–and 3‐Month Immunization Schedules." Journal of Infectious Diseases 177, no. 1 (January 1998): 221–23. http://dx.doi.org/10.1086/517358.

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29

B G, Ranganath. "Incidence of Adverse Events Following Immunization With SA14-14-2 Japanese Encephalitis Vaccine Among Children of 6 to 10Years In Kolar,India." JOURNAL OF CLINICAL AND BIOMEDICAL SCIENCES 01, no. 2 (June 15, 2011): 49–54. http://dx.doi.org/10.58739/jcbs/v01i2.2.

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30

Feroldi, Emmanuel, Chitsanu Pancharoen, Pope Kosalaraksa, Kulkanya Chokephaibulkit, Mark Boaz, Claude Meric, Yanee Hutagalung, and Alain Bouckenooghe. "Primary Immunization of Infants and Toddlers in Thailand with Japanese Encephalitis Chimeric Virus Vaccine in Comparison with SA14-14-2." Pediatric Infectious Disease Journal 33, no. 6 (June 2014): 643–49. http://dx.doi.org/10.1097/inf.0000000000000276.

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31

Yang, Huan, Fengming Fan, Lina Liu, Jie Liu, Yan Sun, Anping Xie, Xiaoling Shi, et al. "A novel amino acid site closely associated with the neurovirulence of live, attenuated Japanese encephalitis vaccine (SA14-14-2 strain)." Vaccine 38, no. 11 (March 2020): 2636–42. http://dx.doi.org/10.1016/j.vaccine.2020.01.005.

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32

Xu, Gaoyuan, Xiaojuan Xu, Zili Li, Qigai He, Bin Wu, Shengfu Sun, and Huanchun Chen. "Construction of recombinant pseudorabies virus expressing NS1 protein of Japanese encephalitis (SA14-14-2) virus and its safety and immunogenicity." Vaccine 22, no. 15-16 (May 2004): 1846–53. http://dx.doi.org/10.1016/j.vaccine.2003.09.015.

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33

Liu, Zheng‐Le, Sean Hennessy, Brian L. Strom, Theodore F. Tsai, Chao‐Min Wan, Sheng‐Cai Tang, Cheng‐Fa Xiang, et al. "Short‐Term Safety of Live Attenuated Japanese Encephalitis Vaccine (SA14–14–2): Results of a Randomized Trial with 26,239 Subjects." Journal of Infectious Diseases 176, no. 5 (November 1997): 1366–69. http://dx.doi.org/10.1086/517323.

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34

Chambers, Thomas J., Deborah A. Droll, Xiaoshan Jiang, William S. M. Wold, and Janice A. Nickells. "JE Nakayama/JE SA14-14-2 virus structural region intertypic viruses: Biological properties in the mouse model of neuroinvasive disease." Virology 366, no. 1 (September 2007): 51–61. http://dx.doi.org/10.1016/j.virol.2007.04.016.

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35

Liu, Xinyu, Yongxin Yu, Maoguang Li, Guodong Liang, Huanyu Wang, Lili Jia, and Guanmu Dong. "Study on the protective efficacy of SA14-14-2 attenuated Japanese encephalitis against different JE virus isolates circulating in China." Vaccine 29, no. 11 (March 2011): 2127–30. http://dx.doi.org/10.1016/j.vaccine.2010.12.108.

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36

Song, Byung-Hak, Gil-Nam Yun, Jin-Kyoung Kim, Sang-Im Yun, and Young-Min Lee. "Biological and genetic properties of SA14-14-2, a live-attenuated Japanese encephalitis vaccine that is currently available for humans." Journal of Microbiology 50, no. 4 (August 2012): 698–706. http://dx.doi.org/10.1007/s12275-012-2336-6.

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37

Wang, Hong-Jiang, Long Liu, Xiao-Feng Li, Qing Ye, Yong-Qiang Deng, E.-De Qin, and Cheng-Feng Qin. "In vitro and in vivo characterization of chimeric duck Tembusu virus based on Japanese encephalitis live vaccine strain SA14-14-2." Journal of General Virology 97, no. 7 (July 1, 2016): 1551–56. http://dx.doi.org/10.1099/jgv.0.000486.

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38

Yang, Huiqiang, Zhushi Li, Hua Lin, Wei Wang, Jian Yang, Lina Liu, Xianwu Zeng, Yonglin Wu, Yongxin Yu, and Yuhua Li. "A novel dengue virus serotype 1 vaccine candidate based on Japanese encephalitis virus vaccine strain SA14-14-2 as the backbone." Archives of Virology 161, no. 6 (March 15, 2016): 1517–26. http://dx.doi.org/10.1007/s00705-016-2817-8.

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39

Nikam, Bhushan Sanjay, Anurag kalia, Suvechchha Pandit, and Nimesh Gupta. "Ablation of regulatory T cells lead to compromised quality of humoral immunity to SA14-14-2 live attenuated Japanese encephalitis vaccine." Journal of Immunology 210, no. 1_Supplement (May 1, 2023): 158.02. http://dx.doi.org/10.4049/jimmunol.210.supp.158.02.

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Abstract:

Abstract Japanese encephalitis (JE) virus is the leading cause of encephalitis in Asia and the western Pacific. Most people infected with JE do not develop symptoms or have only mild symptoms. However, few infected people develop encephalitis and about 1 in 4 cases are fatal. Currently there is no treatment for JE however the vaccines are available. One of the most widely used vaccine against JE is live attenuated SA14-14-2, which is recommended for children and adults. However, less is known about the mechanism by which the vaccine induces protective immunity. We previously found that vaccine-induced CD4+ T cells play crucial role both in protection and in the development of protective humoral immunity. Here, we attempted to understand the role of CD4+ T cell subsets, mainly regulatory T cells (Tregs), in the mechanism of protection conferred by the vaccine. To address this, we used the Treg depletion mouse model and the TCRb −/−mouse as challenge model. We observed that depletion of Tregs lead to enhancement in germinal centre (GC) reaction to vaccine. We found a significant increase in GC-Tfh cells and GC-B cells in Treg ablation condition. We also found an increase in the magnitude of antibodies in response to vaccine particularly the IgG1 isotype. However, as marked by FRNT and the challenge studies, the neutralizing potential of the antibodies was compromised in Treg depleted condition. Altogether, the data suggest that the exclusion of Tregs may enhance the cellular and humoral response, however, that will negatively impact the protective quality of humoral immunity. Overall understanding the immunological mechanism of protective immunity conferred by this vaccine will be essential key for rational design of vaccine against JE or other flaviviruses. NII

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Turtle, Lance, Filippo Tatullo, Tanushka Bali, Vasanthapuram Ravi, Mohammed Soni, Sajesh Chan, Savita Chib, et al. "Cellular Immune Responses to Live Attenuated Japanese Encephalitis (JE) Vaccine SA14-14-2 in Adults in a JE/Dengue Co-Endemic Area." PLOS Neglected Tropical Diseases 11, no. 1 (January 30, 2017): e0005263. http://dx.doi.org/10.1371/journal.pntd.0005263.

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41

Nath, Barnali, Ashutosh Gupta, Siraj A. Khan, and Sachin Kumar. "Enhanced cytopathic effect of Japanese encephalitis virus strain SA14-14-2: Probable association of mutation in amino acid of its envelope protein." Microbial Pathogenesis 111 (October 2017): 187–92. http://dx.doi.org/10.1016/j.micpath.2017.08.046.

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Sricharoenchai, Sirintip, Keswadee Lapphra, Sunate Chuenkitmongkol, Wanatpreeya Phongsamart, Alain Bouckenooghe, Orasri Wittawatmongkol, Supattra Rungmaitree, and Kulkanya Chokephaibulkit. "Immunogenicity of a Live Attenuated Chimeric Japanese Encephalitis Vaccine as a Booster Dose After Primary Vaccination With Live Attenuated SA14-14-2 Vaccine." Pediatric Infectious Disease Journal 36, no. 2 (February 2017): e45-e47. http://dx.doi.org/10.1097/inf.0000000000001395.

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43

Li, Zhushi, Huiqiang Yang, Jian Yang, Hua Lin, Wei Wang, Lina Liu, Yu Zhao, et al. "Construction and preliminary investigation of a novel dengue serotype 4 chimeric virus using Japanese encephalitis vaccine strain SA14-14-2 as the backbone." Virus Research 191 (October 2014): 10–20. http://dx.doi.org/10.1016/j.virusres.2014.07.017.

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Janewongwirot, Pakpoom, Thanyawee Puthanakit, Suvaporn Anugulruengkitt, Watsamon Jantarabenjakul, Chayapa Phasomsap, Sompong Chumket, Sutee Yoksan, and Chitsanu Pancharoen. "Immunogenicity of a Japanese encephalitis chimeric virus vaccine as a booster dose after primary vaccination with SA14-14-2 vaccine in Thai children." Vaccine 34, no. 44 (October 2016): 5279–83. http://dx.doi.org/10.1016/j.vaccine.2016.09.005.

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45

Wang, Ran, Dongying Fan, Lei Wang, Yueqi Li, Hongning Zhou, Na Gao, and Jing An. "Neutralizing antibody rather than cellular immune response is maintained for nearly 20 years among Japanese encephalitis SA14-14-2 vaccinees in an endemic setting." Infection, Genetics and Evolution 85 (November 2020): 104476. http://dx.doi.org/10.1016/j.meegid.2020.104476.

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46

Yamshchikov, Vladimir, Marina Manuvakhova, and Efrain Rodriguez. "Development of a human live attenuated West Nile infectious DNA vaccine: Suitability of attenuating mutations found in SA14-14-2 for WN vaccine design." Virology 487 (January 2016): 198–206. http://dx.doi.org/10.1016/j.virol.2015.10.015.

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47

Wang, Ran, Zida Zhen, Lance Turtle, Baohua Hou, Yueqi Li, Na Wu, Na Gao, Dongying Fan, Hui Chen, and Jing An. "T cell immunity rather than antibody mediates cross-protection against Zika virus infection conferred by a live attenuated Japanese encephalitis SA14-14-2 vaccine." Applied Microbiology and Biotechnology 104, no. 15 (June 15, 2020): 6779–89. http://dx.doi.org/10.1007/s00253-020-10710-z.

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48

Zheng, Xiaoyan, Xiaozheng Yu, Yan Wang, Min Cui, Ran Wang, and Chenghong Yin. "Immune responses and protective effects against Japanese encephalitis induced by a DNA vaccine encoding the prM/E proteins of the attenuated SA14-14-2 strain." Infection, Genetics and Evolution 85 (November 2020): 104443. http://dx.doi.org/10.1016/j.meegid.2020.104443.

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Calvert, Amanda E., Kandice L. Dixon, Mark J. Delorey, Carol D. Blair, and John T. Roehrig. "Development of a small animal peripheral challenge model of Japanese encephalitis virus using interferon deficient AG129 mice and the SA14-14-2 vaccine virus strain." Vaccine 32, no. 2 (January 2014): 258–64. http://dx.doi.org/10.1016/j.vaccine.2013.11.016.

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50

Wills, Mark R., Bijon K. Sil, Jing X. Cao, Y. X. Yu, and Alan D. T. Barrett. "Antigenic characterization of the live attenuated Japanese encephalitis vaccine virus SA14-14-2: a comparison with isolates of the virus covering a wide geographic area." Vaccine 10, no. 12 (January 1992): 861–72. http://dx.doi.org/10.1016/0264-410x(92)90051-k.

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