廣效A/B型流感疫苗的開發

Abstract

季節性流感是一種急性呼吸道症候群由數種在全世界傳播的流行性感冒病毒(Influenza virus)所引起的疾病。大部分的人得到只會有輕微的症狀和發燒並且可以康復。然而，流感病毒對某些族群會引起嚴重的症狀甚至死亡，特別是新生兒、老年人、慢性病患者及缺乏醫療資源的地區。如今，科學家尚未解決對抗未來新型流感病毒疫苗及藥物的需求。世界衛生組織每年都會預測下一年流行哪些流感病毒株，以便準時製作出下一個年度的流感疫苗。這樣設計的季節性流感疫苗可以預防特定的流感病毒株，但這樣限制了疫苗的保護效果，而且必須每年重新製造以針對即將出現的流感病毒株。因此，去研發一個可以保護多種流感病株的廣效型流感疫苗對社會大眾是非常重要的。我的研究目的就是去研發同時具有B型流感病毒血凝集素(Hemagglutinin)和A型流感病毒血凝集素組成的嵌合型血凝集素(Chimeric Hemagglutinin)疫苗作為對抗季節性流感以及尚未出現的新型流感的有效工具。在此研究中，我設計出了特別的嵌合型血凝集素蛋白並將其產出。接續研究了此重組蛋白的構型和評估它的免疫反應。結果顯示了嵌合型血凝集素蛋白可以使免疫系統產生抗體對抗四種主要的流感病毒血凝集素(H1, H3, Victoria, Yamagata)並且可以引起CD4+ and CD8+ T 細胞免疫反應。所以，此種嵌合型血凝集素是具有潛力開發成對付流感病毒感染的廣效型疫苗。

Seasonal influenza is an acute respiratory disease caused by different types of influenza virus which are circulated in all parts of the world. Most people who get influenza can recover from fever and slight symptoms. However, influenza can cause severe illness or even death particularly in newborns, the elderly, and those with underlined disease or without medical treatments. Nowadays, combating the ongoing epidemic influenza is an unmet medical need. Every year the World Health Organization makes predictions on which influenza strains will circulate in the following year so that a vaccine can be designed, manufactured and administered to the public on time. Seasonal influenza vaccines thus designed can protect against specific viral strains but have to be renewed annually to target the upcoming strains, which limits their protective breadth and efficacy. Therefore, developing a universal influenza vaccine which is broadly protective against diverse influenza virus strains would have a great benefit to public health. My research goal is to design a chimeric hemagglutinin (cHA) that contains the head domain from influenza virus B and the stem domain from influenza A to induce broadly protective activity against seasonal influenza and unexpected pandemic influenza. cHA was designed and expressed. The properties of the recombinant protein were further characterized and used for evaluation of the immune response. Moreover, the effects of N-glycosylation on immunogenicity induced by HA nucleoside vaccine were also evaluated. The result showed that cHA protein can elicit significant IgG titer against variants of HA among H1, H3, Vic and Yam and CD8+ and CD4+ T cell response, suggesting that the cHA has the potential to be a universal vaccine.