單醣棘蛋白疫苗對SARS-CoV-2病毒及其變異株之保護力研究

Monoglycosylated Spike Vaccine Provides Better Protection against SARS-CoV-2 and its variants

黃菡頤(Han-Yi Huang)

指導教授 ： 姜至剛

共同指導教授 ： 馬徹(Che Alex Ma)

國立臺灣大學/醫學院/國際三校農業生技與健康醫療碩士學位學程/碩士(2021年)

https://doi.org/10.6342/NTU202103030

摘要

新冠肺炎 (COVID-19) 大流行促使了數百種針對新冠病毒 (SARS-CoV-2) 疫苗的開發。然而，儘管許多世衛組織批准的疫苗已顯示出很高的效力，但最近出現的許多變異株(variant) 造成的疫苗保護力下降進而引起了極大關注。此前，本實驗室所研發之單醣流感血凝素 (HAmg) 疫苗利用去除抗原中的聚醣屏蔽區，暴露了在原始全醣基化中難以接近且不易變異的抗原區域，因而展現較佳的跨病毒株保護力並誘導更好的免疫反應。憑藉流感研究的經驗，本研究研發出重組單醣棘蛋白 (Smg) 作為新冠肺炎疫苗，並分析其特性和免疫原性。疫苗開發主要目標的新冠病毒棘蛋白是一種高度醣化的病毒表面蛋白，在去除聚醣屏蔽後，Smg 可以激發更多針對病毒變異株之間不易變異抗原位的抗體。我們在小鼠、倉鼠和人類血管收縮素轉化酶2 (hACE2) 基因轉殖小鼠中進行疫苗接種實驗，並用酵素免疫分析法 (ELISA) 分析棘蛋白與抗體結合能力、免疫血清的中和效力以及病毒感染的保護作用時，發現 Smg 可以引發針對新冠病毒變異株更好的免疫反應，並有很大潛力成為對抗新冠肺炎更強大的武器。

關鍵字

新冠肺炎 ； 疫苗 ； 變異株 ； 新冠病毒棘蛋白

並列摘要

COVID-19 pandemic has encouraged the development of hundreds of vaccines against SARS-CoV-2. However, although many WHO-approved vaccines have shown high efficacy, the recent emergence of novel variants which can escape from the serum antibodies of the immunized individuals has raised significant concerns. Previously, our lab demonstrated that monoglycosylated influenza hemagglutinins (HAmg) vaccine can provide cross-strain protection and induce better immune responses, because the removal of glycan shields in antigens exposed more conserved antigenic regions which were hard to access in the original fully-glycosylated protein. With experience in influenza studies, we designed the recombinant monoglycosylated spike (Smg) as a vaccine for SARS-CoV-2 and analyzed its properties and immunogenicity. SARS-CoV-2 spike protein is an extensively glycosylated viral fusion protein and is the main target for vaccine development. After the glycan shield removal, Smg can provoke more antibodies targeting the epitopes which are conserved between virus variants. Indeed, as we performed the vaccination experiments in mice, hamster and hACE2 transgenic mice and analyzed the spike binding titer with ELISA, the neutralization potency of the immunized serum, and also protection against SARS-CoV-2 in vivo, we found that Smg can elicit better immune responses against SARS-CoV-2 variants and have great potential to be a more powerful weapon in the battle against COVID-19.

並列關鍵字

COVID-19 ； vaccine ； variants ； SARS-CoV-2 spike

參考文獻

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