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Study on Infection Animal Model and Mucosal Adjuvant for the Development of Hand-Foot-Mouth Disease Vaccine
- Author(s)
- 이은제
- Advisor
- 장선영
- Department
- 일반대학원 약학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2023-08
- Language
- kor
- Keyword
- Adjuvant; Coxsackievirus A16; Enterovirus 71; HFMD; Mucosal vaccine; Vaccine
- Alternative Abstract
- Hand-foot-mouth disease (HFMD) is a viral infectious disease that occurs in children under 5 years of age. It is highly contagious and is mainly spread through direct contact with saliva, bodily fluids, or feces. HFMD shows symptoms such as a blistering rash around the hands, feet, and mouth. The main causes of HFMD are coxsackievirus A16 (CVA16) and enterovirus71 (EV71). CVA16 is the most important causative virus and in severe cases causes myocarditis and pneumonia in adults. Enterovirus is the second major causative virus and has a lower incidence than coxsackievirus, but in severe cases, it leads to central nervous system infection and death. <br>The EV71 C4a, a dominant sub-genotype in Korea, China, and Taiwan, has the disadvantage of not infecting wild-type mice. To overcome these drawbacks, hSCARB2 transgenic mice were used. Monovalent and bivalent antisera effectively protected against EV71 C4a and CVA16 infection, and high-dose bivalent antiserum showed 100% survival against both viruses. Monovalent and bivalent antisera reduced brainstem viral RNA in EV71 C4a infection and decreased brainstem and muscle viral RNA in the CVA16 virus. <br>Mongolian gerbils were used to confirm the protective ability against viral infection by active immunity after vaccination. Mongolian gerbils were vaccinated bivalently with a mixture of inactivated EV71 and inactivated CVA16. As a result of antibody production and cytokine analysis after vaccination, antigen-specific IgG production was effectively induced, and cytokine levels were also increased at high doses. Bivalent vaccination protected against EV71 C4a and CVA16 virus infection in a dose-dependent manner. In addition, because of confirming viral RNA in the brainstem, muscle, heart, and spleen, all immunization groups significantly decreased, and tissue staining also alleviated heart and muscle damage in a dose-dependent manner. <br>Because enteroviruses are primarily transmitted via the fecal-oral route and target the gastrointestinal epithelium, the development of mucosal vaccines has also been attempted. The first line of defense, the mucosal surface in contact with the external environment, protects the body from infection by various microorganisms. Injectable vaccines also induce T cell immune responses and systemic immunity that produces serum IgG, but mucosal immunity by mucosal vaccines also induces various mucosal immune responses, including systemic immunity and secretory IgA. <br>Curdlan, a 1-3- glucan, exhibits potent immunostimulatory effects when delivered as a vaccine adjuvant. Concomitant administration of curdlan and OVA increased the production of OVA-specific IgG and IgA antibodies in serum and mucosal secretions. In addition, differentiation of OVA-specific Th1/Th17 cells was induced. Intranasal administration of enterovirus recombinant VP1 protein mixed with curdlan induced a VP1-specific Th17 immune response. Antiserum mixed with VP1 and curdlan effectively protected against EV71 C4a infection. In Mongolian gerbils, intranasal administration of VP1 and curdlan effectively protected against EV71 C4a infection. It also reduced viral titers in muscle, brainstem, and spleen, and prevented muscle damage. <br>In this study, hSCARB2 transgenic mice and Mongolian gerbils were used as animal models for the development of a vaccine for HFMD. It was confirmed that infection of EV71 C4a and CVA16 was protected by passive immunization in hSCARB2 transgenic mice. Mongolian gerbils were used to induce active immunity by vaccination. Antibody production and cytokine production were effectively induced in Mongolian gerbils when the bivalently inactivated virus was vaccinated.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Pharmacy > 4. Theses(Ph.D)
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