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發展高產量桿狀病毒表現系統以生產腸病毒類病毒顆粒疫苗
Dissertation

發展高產量桿狀病毒表現系統以生產腸病毒類病毒顆粒疫苗

林事曄
Doctor of Philosophy (PHD), 國立清華大學, 化學工程學系
2013

Abstract

腸病毒 腸病毒71型 桿狀病毒 類病毒顆粒 疫苗 enterovirus EV71 baculovirus virus-like particle VLP vaccine
Enterovirus 71 (EV71) is one of the causative pathogens of hand-foot-and-mouth disease which leads to a major public health issue across the Asia-Pacific region. It mostly affects children and causes severe neurological complications and even death. Since 1998, three EV71 epidemics have occurred in Taiwan, resulting in hundreds of cases with severe complications and entailing the need to develop vaccines against EV71. Using the recombinant baculovirus/insect cell expression vector system, we have developed an EV71 vaccine candidate based on virus-like particle (VLP) that resembles the authentic virus in size, shape and composition and can elicit anti-viral immune response in animal model. In this study we developed new baculovirus constructs in order to improve the VLP yield and quality. We next evaluated the immune responses elicited by the purified EV71 VLP and comfirmed the cross neutralization of immune serum with other enteroviruses of different genotypes. With the improved recombinant baculovirus design, we produced enterovirus VLPs of EV71 C4, B5 and Coxsackievirus A16 (CV A16) to develop a broad-spectrum vaccine candidate against enterovirus infection. We confirmed the formation of these VLPs with correct compostion of 3 viral proteins. In the future, we will evaluate the immunogenicity of combined VLP antigens of different enterovirus and further prove the broad protection of the multitypic VLP vaccine against viral challenge in mouse model.

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