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Decreases in Both the Seroprevalence of Serum Antibodies and Seroprotection against Japanese Encephalitis Virus among Vaccinated Children

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Virologica Sinica

Abstract

The incidence of Japanese encephalitis (JE) has significantly decreased in China due to JE vaccines. In this study, we investigated the post-JE vaccination seroprevalence and protection provided by vaccinated sera against Japanese encephalitis virus (JEV) to elucidate the persistence and waning of antibodies to JEV among JE-SA14-14-2-vaccinated children. A total of 300 serum samples were collected from vaccinated children aged 3–10 years in Zhaotong, Yunnan, China. The seroprevalence of anti-JEV antibodies was determined by enzyme-linked immune sorbent assay and plaque reduction neutralization test. The highest seropositivity of 82% was observed in vaccinated children during the first 0.5–1.5 years after booster vaccination. Then, the seropositivity began to decline and remained lower than the original level observed in the 0.5–1.5-year group. An association was found between the waning of seroprevalence and elapsed time of the post-booster vaccination. Similarly, the neutralizing antibody (nAb) titres gradually decreased over time, and the levels showed a positive correlation with the protective efficacy in mice. This finding suggests that nAbs play an important role in the antiviral process and that the nAb titre is an adequately credible parameter for evaluating the protective efficacy induced by the JE vaccine. Our results provide data that clarify the persistence and waning of antibodies to JEV, which may help elucidate the pathogenesis of JE.

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References

  • Baldovin T, Mel R, Bertoncello C, Carpene G, Soppelsa F, Giliberti A, Baldo V (2012) Persistence of immunity to tick-borne encephalitis after vaccination and natural infection. J Med Virol 84:1274–1278

    Article  CAS  Google Scholar 

  • Buddhari D, Aldstadt J, Endy TP, Srikiatkhachorn A, Thaisomboonsuk B, Klungthong C, Nisalak A, Khuntirat B, Jarman RG, Fernandez S, Thomas SJ, Scott TW, Rothman AL, Yoon IK (2014) Dengue virus neutralizing antibody levels associated with protection from infection in thai cluster studies. PLoS Negl Trop Dis 8:e3230

    Article  Google Scholar 

  • Campbell GL, Hills SL, Fischer M, Jacobson JA, Hoke CH, Hombach JM, Marfin AA, Solomon T, Tsai TF, Tsu VD, Ginsburg AS (2011) Estimated global incidence of Japanese encephalitis: a systematic review. Bull World Health Organ 89(766–774):774A–774E

    Google Scholar 

  • Gao X, Li X, Li M, Fu S, Wang H, Lu Z, Cao Y, He Y, Zhu W, Zhang T, Gould EA, Liang G (2014) Vaccine strategies for the control and prevention of Japanese encephalitis in Mainland China, 1951–2011. PLoS Negl Trop Dis 8:e3015

    Article  Google Scholar 

  • Hegde NR, Gore MM (2017) Japanese encephalitis vaccines: immunogenicity, protective efficacy, effectiveness, and impact on the burden of disease. Hum Vaccines Immunother 13:1–18

    Article  Google Scholar 

  • Hombach J, Solomon T, Kurane I, Jacobson J, Wood D (2005) Report on a WHO consultation on immunological endpoints for evaluation of new Japanese encephalitis vaccines, WHO, Geneva, 2–3 September, 2004. Vaccine 23:5205–5211

    Article  Google Scholar 

  • Hsu LC, Chen YJ, Hsu FK, Huang JH, Chang CM, Chou P, Lin IF, Chang FY (2014) The incidence of Japanese encephalitis in Taiwan—a population-based study. PLoS Negl Trop Dis 8:e3030

    Article  Google Scholar 

  • Khan SA, Kakati S, Dutta P, Chowdhury P, Borah J, Topno R, Jadhav SM, Mohapatra PK, Mahanta J, Gupte MD (2016) Immunogenicity & safety of a single dose of live-attenuated Japanese encephalitis vaccine SA 14-14-2 in adults. Indian J Med Res 144:886–892

    Article  Google Scholar 

  • Konishi E, Ajiro N, Nukuzuma C, Mason PW, Kurane I (2003) Comparison of protective efficacies of plasmid DNAs encoding Japanese encephalitis virus proteins that induce neutralizing antibody or cytotoxic T lymphocytes in mice. Vaccine 21:3675–3683

    Article  CAS  Google Scholar 

  • Konishi E, Kitai Y, Tabei Y, Nishimura K, Harada S (2010) Natural Japanese encephalitis virus infection among humans in west and east Japan shows the need to continue a vaccination program. Vaccine 28:2664–2670

    Article  Google Scholar 

  • Lee DW, Choe YJ, Kim JH, Song KM, Cho H, Bae GR, Lee JK (2012) Epidemiology of Japanese encephalitis in South Korea, 2007–2010. Int J Infect Dis 16:e448–e452

    Article  Google Scholar 

  • Lee EY, Kim JY, Lee DK, Yoon IS, Ko HL, Chung JW, Chang J, Nam JH (2016) Sublingual immunization with Japanese encephalitis virus vaccine effectively induces immunity through both cellular and humoral immune responses in mice. Microbiol Immunol 60:846–853

    Article  CAS  Google Scholar 

  • Li X, Ma SJ, Liu X, Jiang LN, Zhou JH, Xiong YQ, Ding H, Chen Q (2014) Immunogenicity and safety of currently available Japanese encephalitis vaccines: a systematic review. Hum Vaccin Immunother 10:3579–3593

    Article  Google Scholar 

  • Li X, Cui S, Gao X, Wang H, Song M, Li M, Fu S, Lv Z, He Y, Lei W, Wang B, Lu X, Liang G (2016) The spatio-temporal distribution of Japanese encephalitis cases in different age groups in Mainland China, 2004–2014. PLoS Negl Trop Dis 10:e0004611

    Article  Google Scholar 

  • Liu X, Yu Y, Li M, Liang G, Wang H, Jia L, Dong G (2011) Study on the protective efficacy of SA14-14-2 attenuated Japanese encephalitis against different JE virus isolates circulating in China. Vaccine 29:2127–2130

    Article  CAS  Google Scholar 

  • Luo D, Yin H, Xili L, Song J, Wang Z (1994) The efficacy of Japanese encephalitis vaccine in Henan, China: a case-control study. Southeast Asian J Trop Med Public Health 25:643–646

    CAS  PubMed  Google Scholar 

  • Mansfield KL, Hernandez-Triana LM, Banyard AC, Fooks AR, Johnson N (2017) Japanese encephalitis virus infection, diagnosis and control in domestic animals. Vet Microbiol 201:85–92

    Article  Google Scholar 

  • Misra UK, Kalita J (2010) Overview: Japanese encephalitis. Prog Neurobiol 91:108–120

    Article  CAS  Google Scholar 

  • Monath TP, Fowler E, Johnson CT, Balser J, Morin MJ, Sisti M, Trent DW (2011) An inactivated cell-culture vaccine against yellow fever. N Engl J Med 364:1326–1333

    Article  CAS  Google Scholar 

  • Ohrr H, Tandan JB, Sohn YM, Shin SH, Pradhan DP, Halstead SB (2005) Effect of single dose of SA 14-14-2 vaccine 1 year after immunisation in Nepalese children with Japanese encephalitis: a case-control study. Lancet 366:1375–1378

    Article  CAS  Google Scholar 

  • Oya A (1988) Japanese encephalitis vaccine. Acta Paediatr Jpn 30:175–184

    Article  CAS  Google Scholar 

  • Pan JR, Yan JY, Zhou JY, Tang XW, He HQ, Xie RH, Mao HY, Zhang YJ, Xie SY (2016) Sero-molecular epidemiology of Japanese encephalitis in Zhejiang, an eastern province of China. PLoS Negl Trop Dis 10:e0004936

    Article  Google Scholar 

  • Saxena V, Dhole TN (2008) Preventive strategies for frequent outbreaks of Japanese encephalitis in Northern India. J Biosci 33:505–514

    Article  Google Scholar 

  • Simon LV, Kruse B (2017) Encephalitis, Japanese. StatPearls, Treasure Island

    Google Scholar 

  • Sirivichayakul C, Sabchareon A, Limkittikul K, Yoksan S (2014) Plaque reduction neutralization antibody test does not accurately predict protection against dengue infection in Ratchaburi cohort. Thailand. Virol J 11:48

    Article  Google Scholar 

  • Sohn YM, Tandan JB, Yoksan S, Ji M, Ohrr H (2008) A 5-year follow-up of antibody response in children vaccinated with single dose of live attenuated SA14-14-2 Japanese encephalitis vaccine: immunogenicity and anamnestic responses. Vaccine 26:1638–1643

    Article  CAS  Google Scholar 

  • Solomon T, Dung NM, Kneen R, Gainsborough M, Vaughn DW, Khanh VT (2000) Japanese encephalitis. J Neurol Neurosurg Psychiatry 68:405–415

    Article  CAS  Google Scholar 

  • Tandale BV, Khan SA, Kushwaha KP, Rahman H, Gore MM, Japanese Encephalitis Vaccination Efficacy Case Control Study G (2018) Effectiveness of Japanese encephalitis SA 14-14-2 live attenuated vaccine among Indian children: retrospective 1:4 matched case-control study. J Infect Public Health 11:713–719

    Article  Google Scholar 

  • Tseng HF, Tan HF, Chang CK, Huang WL, Ho WC (2003) Seroepidemiology study of Japanese encephalitis neutralizing antibodies in southern Taiwan: a comparative study between urban city and country townships. Am J Infect Control 31:435–440

    Article  Google Scholar 

  • Turtle L, Tatullo F, Bali T, Ravi V, Soni M, Chan S, Chib S, Venkataswamy MM, Fadnis P, Yaich M, Fernandez S, Klenerman P, Satchidanandam V, Solomon T (2017) Cellular immune responses to live attenuated Japanese encephalitis (JE) vaccine SA14-14-2 in adults in a JE/dengue co-endemic area. PLoS Negl Trop Dis 11:e0005263

    Article  Google Scholar 

  • Upreti SR, Lindsey NP, Bohara R, Choudhary GR, Shakya S, Gautam M, Giri JN, Fischer M, Hills SL (2017) Updated estimation of the impact of a Japanese encephalitis immunization program with live, attenuated SA 14-14-2 vaccine in Nepal. PLoS Negl Trop Dis 11:e0005866

    Article  Google Scholar 

  • Van Gessel Y, Klade CS, Putnak R, Formica A, Krasaesub S, Spruth M, Cena B, Tungtaeng A, Gettayacamin M, Dewasthaly S (2011) Correlation of protection against Japanese encephalitis virus and JE vaccine (IXIARO(R)) induced neutralizing antibody titers. Vaccine 29:5925–5931

    Article  Google Scholar 

  • Wang H, Liang G (2015) Epidemiology of Japanese encephalitis: past, present, and future prospects. Ther Clin Risk Manag 11:435–448

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang R, Liao X, Fan D, Wang L, Song J, Feng K, Li M, Wang P, Chen H, An J (2018) Maternal immunization with a DNA vaccine candidate elicits specific passive protection against post-natal Zika virus infection in immunocompetent BALB/c mice. Vaccine 36:3522–3532.

    Article  CAS  Google Scholar 

  • Wu CJ, Huang HW, Tao MH (2003) Induction of cross-protection against two wild-type Taiwanese isolates of Japanese encephalitis virus using Beijing-1 strain DNA vaccine. Vaccine 21:3938–3945

    Article  CAS  Google Scholar 

  • Xin YY, Ming ZG, Peng GY, Jian A, Min LH (1988) Safety of a live-attenuated Japanese encephalitis virus vaccine (SA14-14-2) for children. Am J Trop Med Hyg 39:214–217

    Article  CAS  Google Scholar 

  • Zhang L, Luan RS, Jiang F, Rui LP, Liu M, Li YX, Yin ZD, Luo HM (2012) Epidemiological characteristics of Japanese encephalitis in Guizhou Province, China, 1971–2009. Biomed Environ Sci 25:297–304

    PubMed  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (81471957, 81772172, 81671971, U1602223 and 81871641) and a grant from the Open Research Projects of Key Laboratory of Beijing Ditan Hospital, Capital Medical University (DTKF201705). These funding sources played no part in the decision to publish, data analysis, or writing of the manuscript.

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Author notes

  1. Ran Wang and Lyu Xie have contributed equally to this work.

Authors and Affiliations

  1. Department of Microbiology, School of Basic Medical Sciences, Chinese Capital Medical University, Beijing, 100069, China

    Ran Wang, Na Gao, Dongying Fan, Hui Chen, Peigang Wang & Jing An

  2. Yunnan Provincial Key Laboratory of Vector-borne Disease Control and Research, Yunnan Institute of Parasitic Diseases, Pu’er, 665000, China

    Lyu Xie & Hongning Zhou

  3. Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing, 100069, China

    Jing An

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  1. Ran Wang
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  2. Lyu Xie
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  4. Dongying Fan
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Contributions

RW designed and performed the experiments, analysed the data and wrote the manuscript; LX collected serum samples, demographic information from the vaccinated children and informed consent; NG analysed the data. DF contributed reagents and materials; HC and PW helped with the experiments; HZ designed the research and organized the collaboration; JA principally designed the experiments, revised the manuscript, organized the collaboration and directed the project. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Hongning Zhou or Jing An.

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Conflict of interest

The authors declare that there are no competing interests.

Animal and Human Rights Statement

All animal experiments were performed under approval of the Institutional Animal Care and Use Committee of Chinese Capital Medical University. All animal experiments were performed under diethyl ether anaesthesia, and all efforts were made to minimize suffering. This study was performed in strict accordance with institutional review board approval from the Ethics Committee of Yunnan Institute of Parasitic Diseases, China. Written informed consent for serum sample collection was obtained from the parents or legal guardians on behalf of the vaccinated children. Their guardians completed questionnaires including demographic information and their integrated JE vaccination history. According to records from the local Centre for Disease Control and Prevention, these children had received two doses of the SA14-14-2 JE vaccine (Chengdu Institute of Biological Products, China).

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Wang, R., Xie, L., Gao, N. et al. Decreases in Both the Seroprevalence of Serum Antibodies and Seroprotection against Japanese Encephalitis Virus among Vaccinated Children. Virol. Sin. 34, 243–252 (2019). https://doi.org/10.1007/s12250-019-00099-z

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