2023-08-012024-05-13https://scholars.lib.ntu.edu.tw/handle/123456789/651454由SARS-CoV-2所引起之COVID-19疫情已蔓延全球，造成巨大的公衛威脅與經濟損失。病毒的快速變異使疫苗的效力不斷下降，既有的抗體藥物也相繼失效。SARS-CoV-2之Spike (S) protein (S蛋白)，由S1 subunit (含有receptor binding domain；RBD) 與S2 subunit所組成，能協助病毒感染細胞，因而成為中和抗體與疫苗之主要標的。本計畫將研究由自行研發之Anti-S2單株抗體所組成之融合型與雜合型之中和抗體及抗體雞尾酒療法，是否能提升對SARS-CoV-2之中和力，且能防止病毒產生突變或免疫逃脫，並分析這些新型之中和抗體對不同SARS-CoV-2變異株之病毒中和力。我們也將以病毒感染細胞所必需之RBD與S2的保守功能區塊，包含FP、Heptad Repeat 1、Heptad Repeat 2與Connection Domain等片段，搭配不同之佐劑組成廣效性次單位疫苗，並以小鼠動物模式研究疫苗誘導出之血清對不同病毒變異株之中和抗體力價，與追蹤疫苗效力之持久性等。本計畫涵蓋治療與預防等面向，其研究成果將對COVID-19之廣效性中和抗體、抗體雞尾酒療法與疫苗研發之基礎科學研究與醫藥應用具有重大貢獻。 The COVID-19 pandemic caused by SARS-CoV-2 has spread worldwide, and the public health threats and economic losses are immeasurable. The rapid mutation of SARS-CoV-2 makes the efficacy of vaccines continue to decline, and the existing antibody drugs have also lost effectiveness. The spike (S) protein of SARS-CoV-2 plays an essential role in virus infection and cell entry, and is composed of S1 subunit and S2 subunit, with the receptor-binding domain (RBD) located within the S1. Thus, S protein becomes the main target of neutralizing antibodies and vaccines. This project will study whether the antibody cocktail therapy, composed of the Anti-S2 monoclonal antibodies (mAbs) developed in our laboratory, can enhance the virus neutralization ability and prevent the virus from gene mutation or immune escape, and analyze the virus neutralizing potency of these novel neutralizing Abs against different SARS-CoV-2 variants. We will also use the conserved functional domains of RBD and S2, including the important fragments of FP, Heptad Repeat 1, Heptad Repeat 2, and Connection Domain, to form a broad-effective subunit vaccine with different adjuvants. The mouse animal model will be applied to study the neutralizing antibody titers of antisera elicited by vaccination against different virus strains, and monitor the persistence and sustainability of the vaccine efficacy. This project covers the subjects and strategies in treatment and prevention of COVID-19, and the research results will contribute to the basic scientific research and medical applications in COVID-19 broadly neutralizing antibody, antibody cocktail therapy and vaccine development.SARS-CoV-2;COVID-19;中和抗體;抗體雞尾酒;棘蛋白;SARS-CoV-2; COVID-19; neutralizing antibody; antibody cocktail; Spike protein