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A Bivalent Inactivated Vaccine Prevents Enterovirus 71 and Coxsackievirus A16 Infections in the Mongolian Gerbil
Eun-Je Yi1, Young-In Kim1, Seung-Yeon Kim2
1Laboratory of Microbiology, College of Pharmacy, and Research Institute of Pharmaceutical Science and Technology (RIPST), Ajou University, Suwon 16499, Republic of Korea.
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.
Insights
A new bivalent vaccine combining inactivated Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) shows promise for preventing hand-foot-and-mouth disease (HFMD) in children. Studies indicate it boosts antibody production and protects against severe symptoms.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Hand-foot-and-mouth disease (HFMD) is a common viral illness in young children, primarily caused by coxsackievirus (CV) and enterovirus (EV).
- Current therapeutic options for HFMD are limited, highlighting the need for effective preventive strategies like vaccination.
- Developing a bivalent vaccine targeting multiple EV strains, such as EV71 and CVA16, is crucial for broad protection.
Purpose of the Study:
- To evaluate the efficacy of a bivalent inactivated vaccine against Enterovirus 71 (EV71) and Coxsackievirus A16 (CVA16) in a Mongolian gerbil model.
- To assess the vaccine's ability to induce immune responses, protect against viral challenge, and mitigate disease symptoms.
Main Methods:
- Mongolian gerbils were immunized with a bivalent inactivated EV71 C4a and CVA16 vaccine at varying doses.
- Humoral immunity was assessed by measuring Ag-specific IgG antibody production.
- Cellular immunity was evaluated by analyzing T cell-biased cytokine gene expression (Th1, Th2, Th17).
- Vaccine efficacy was determined by challenging immunized gerbils with live viruses, monitoring for paralytic signs, survival rates, viral RNA load in organs, and histological tissue damage.
Main Results:
- Bivalent vaccine immunization significantly increased EV71- and CVA16-specific IgG antibody levels in a dose-dependent manner.
- High-dose immunization strongly activated Th1, Th2, and Th17 immune responses.
- Vaccination mitigated paralytic symptoms, increased survival rates, and significantly reduced viral RNA loads in various organs post-challenge.
- Histological examination revealed that the vaccine alleviated EV71 and CVA16-induced tissue damage in the heart and muscle.
Conclusions:
- The bivalent inactivated EV71 C4a/CVA16 vaccine is a safe and effective candidate for preventing HFMD.
- The vaccine demonstrates potential for broad protection against major HFMD-causing enteroviruses.
- Further research and clinical trials are warranted to confirm its efficacy in human populations.
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