Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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A Bivalent Inactivated Vaccine Prevents Enterovirus 71 and Coxsackievirus A16 Infections in the Mongolian Gerbil

  • Eun-Je Yi (Laboratory of Microbiology, College of Pharmacy, and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University) ;
  • Young-In Kim (Laboratory of Microbiology, College of Pharmacy, and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University) ;
  • Seung-Yeon Kim (Department of Biomedical Sciences, Graduate School of Ajou University) ;
  • Sung Hyun Ahn (HK inno.N BIO Research Institute, BIO-Pharmaceutical Research Center) ;
  • Hyoung Jin Lee (HK inno.N BIO Research Institute, BIO-Pharmaceutical Research Center) ;
  • Bohyun Suh (HK inno.N BIO Research Institute, BIO-Pharmaceutical Research Center) ;
  • Jaelim Yu (HK inno.N BIO Research Institute, BIO-Pharmaceutical Research Center) ;
  • Jeehye Park (HK inno.N BIO Research Institute, BIO-Pharmaceutical Research Center) ;
  • Yoon Jung Lee (HK inno.N BIO Research Institute, BIO-Pharmaceutical Research Center) ;
  • Eunju Jung (HK inno.N BIO Research Institute, BIO-Pharmaceutical Research Center) ;
  • Sun-Young Chang (Laboratory of Microbiology, College of Pharmacy, and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University)
  • Received : 2023.03.15
  • Accepted : 2023.03.27
  • Published : 2023.05.01
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Abstract

Hand-foot-and-mouth disease (HFMD) is a viral infectious disease that occurs in children under 5 years of age. Its main causes are coxsackievirus (CV) and enterovirus (EV). Since there are no efficient therapeutics for HFMD, vaccines are effective in preventing the disease. To develop broad coverage against CV and EV, the development of a bivalent vaccine form is needed. The Mongolian gerbil is an efficient and suitable animal model of EV71 C4a and CVA16 infection used to investigate vaccine efficacy following direct immunization. In this study, Mongolian gerbils were immunized with a bivalent inactivated EV71 C4a and inactivated CVA16 vaccine to test their effectiveness against viral infection. Bivalent vaccine immunization resulted in increased Ag-specific IgG antibody production; specifically, EV71 C4a-specific IgG was increased with medium and high doses and CVA16-specific IgG was increased with all doses of immunization. When gene expression of T cell-biased cytokines was analysed, Th1, Th2, and Th17 responses were found to be highly activated in the high-dose immunization group. Moreover, bivalent vaccine immunization mitigated paralytic signs and increased the survival rate following lethal viral challenges. When the viral RNA content was determined from various organs, all three doses of bivalent vaccine immunization were found to significantly decrease viral amplification. Upon histologic examination, EV71 C4a and CVA16 induced tissue damage to the heart and muscle. However, bivalent vaccine immunization alleviated this in a dose-dependent manner. These results suggest that the bivalent inactivated EV71 C4a/CVA16 vaccine could be a safe and effective candidate HFMD vaccine.

Keywords

Acknowledgement

This study was supported by the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT and future Planning [NRF-2020R1A2B5B01001690, NRF-2022R1I1A1A01069464], Ministry of Health and Welfare of Korea [HI17C0047] and HK inno.N [2020C208900001].

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