至今中國總共有三間生物公司的疫苗踏入Phase3狀態,包括為Cansino、Sinovac及Sinopharm。765Please respect copyright.PENANA7h8ykHnFas
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其中Sinovac (Phase 3地點:巴西)及國營的Sinopharm(Ref2) (Phase 3地點:阿聯酋)兩間均用上滅活病毒疫苗(Inactivated Virus Vaccine)設計,本文將會就此作深入探討。765Please respect copyright.PENANAL8XJpCElGC765Please respect copyright.PENANAAgABBgEM2K
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(圖1)滅活病毒疫苗,顧名思義就是將病毒除去感染能力,當作疫苗之用。765Please respect copyright.PENANARrPbhM0s4A
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下列為Sinovac製作滅活病毒疫苗的扼要流程(Ref3)765Please respect copyright.PENANA429G5jHP4t
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1.從一名進入深切治療部的中國病患肺部體液中抽取病毒。765Please respect copyright.PENANAXzb3JxzaD7
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2.經過數輪實驗室細胞的培植,使病毒數量增加。765Please respect copyright.PENANAvihY8Yb6NT
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3.加入化學物消減病毒的感染力和多重過濾,取得弱化的武肺病毒。765Please respect copyright.PENANAXBmlkjrG39
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4.將其製成可注射的疫苗。765Please respect copyright.PENANAS1XdAS3JS8
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(圖2)將滅活病毒疫苗注射到身體後,身體的免疫細胞便會製作對應弱化病毒的抗體。765Please respect copyright.PENANAaBEsjLcSGN
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在繼續講述抗體之前,可先閱覽(圖3)溫故知新一下武肺入侵人體細胞的簡要過程,又或者可以到之前我所寫的文章觀看略為詳細的版本。765Please respect copyright.PENANAq6lN9KxTcp
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(圖4)抗體(Antibody)頂多只能阻礙病毒進入細胞或者指示其他免疫細胞前來清滅病毒,並無獨立能力清滅病毒。765Please respect copyright.PENANALnhDpqLLmK
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而能夠阻礙病毒進入細胞的抗體,我們將稱之為Neutralizing Antibody,而圖中已列出其中的兩款機制。765Please respect copyright.PENANAhP8PiCfnc3
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1.抗體與病毒的S protein合併,765Please respect copyright.PENANAJ2w1frbI3F
防止條件1的達成。765Please respect copyright.PENANA5LTrOWjiMp
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2.抗體與病毒其他位置合併,765Please respect copyright.PENANA2VZXGB8mq5
防止條件3的達成。765Please respect copyright.PENANAfYWBhuhk4Y
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(圖5)用上滅活病毒疫苗的話,抗體的製作便會針對病毒的各個位置而進行。765Please respect copyright.PENANA6O3CNTknOd
基於並非所有抗體也能夠拼合在病毒的關鍵位置,不能夠阻礙病毒進入細胞的抗體,我們將稱之為Non-Neutralizing Antibody。765Please respect copyright.PENANAzgcN7gZe5l
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不過,就算是Non-Neutralizing Antibody,它亦能有能力標示病毒,指引其他免疫細胞前來清滅病毒。765Please respect copyright.PENANAw8ule9gDIg
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(圖6)Non-Neutralizing Antibody的出現,將會引伸出一個名為Antibody Dependent Enhancement(ADE)的重要問題;765Please respect copyright.PENANAghJ1zHFciu
簡單來說,就是抗體適得其反地協助病毒入侵人體細胞。765Please respect copyright.PENANAd9WnKCQFdq
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免疫細胞的表面上,有著接收器識辨抗體的某個區域。765Please respect copyright.PENANAmDXb6Ul7nu
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但若果有過多Non-Neutralizing Antibody黏在病毒裡頭的話,病毒就有機會可以無視之前那3條法則,不需要經過ACE2,而是透過免疫細胞的表面上識辨抗體的接收器進入細胞。765Please respect copyright.PENANA4npTKJwhEc
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換句話說,抗體在這情況下變相成為幫兇或者25仔,輔助病毒進入細胞,這現象我們稱之為ADE。765Please respect copyright.PENANAqZOS5bLil8
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(圖7)武肺病毒進入細胞後,需要切割S protein才能夠開始進行繁殖工作。765Please respect copyright.PENANASppPW3ae8Y
所以就算有Non-Neutralizing antibody做25仔,如果病毒幸運地有Neutralizing antibody保護S protein免受切割的話,病毒依舊無法作惡。765Please respect copyright.PENANAxo1Mqzru0g
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但若果無Neutralizing antibody保護的話,病毒就會利用免疫細胞作為寄主,避開一切免疫機制,大量製造病毒。765Please respect copyright.PENANABopyAT7ofT
情形就好像本身理應維護法紀的警察,突然之間搖身一變成為罪惡的溫床,窩藏及協助罪犯(病毒)滋生,導致情況一發不可收拾。765Please respect copyright.PENANAL2bAdLH4iB
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(圖8)ADE這現象,科學家一直以來均有記錄及研究。(Ref4)765Please respect copyright.PENANA5KklqXlPAn
以登革熱為例,病人染上登革熱病毒(Dengue Virus)的話,身體便會製造登革熱病毒抗體。765Please respect copyright.PENANAMZYHmHz3dV
但基於登革熱病毒與寨卡病毒(Zika Virus)有頗為相似的地方,某部份的登革熱病毒抗體「幸運地」便成為寨卡病毒的Non-Neutralizing Antibody,透過ADE幫忙寨卡病毒入侵人體。765Please respect copyright.PENANALpL6fI2rZP
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亦即是說,擁有登革熱病毒抗體的人反而更有機會受到寨卡病毒入侵。765Please respect copyright.PENANAcp0N3XugaZ
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(圖9)有研究指出,03年SARS病毒亦會依靠未曾上市的疫苗所產生出的Non-Neutralizing Antibody,不需經過ACE2便能入侵免疫細胞。(Ref5)765Please respect copyright.PENANAC4Lxz3zKnf
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武肺會否出現同樣現象,暫時尚未清楚。765Please respect copyright.PENANAr664bCDsmi
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只不過各國進行Phase3中的疫苗,大多也是針對著武肺病毒S protein位置而設計,故此出現Non-Neutralizing antibody將會比用上整個武肺病毒而作為疫苗設計的那兩間公司為低,ADE的機率亦相對減少。765Please respect copyright.PENANAjyS0iJF9XW
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當然,另一方面來看,中國那兩間公司因為用上整個武肺病毒來設計疫苗,理論上所產生的抗體數量及濃度亦會為高,抵抗的效果亦會相對顯著,但ADE的機率出現亦會相對為高。765Please respect copyright.PENANAJy5rHTxeIB
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美國Moderna已表示Phase3的報告將會探討ADE的可能,但願中國Sinovac及國營Sinopharm的Phase3報告,也會在ADE方面進行深入探討吧!765Please respect copyright.PENANAwotOAcEYIB
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Ref2:https://jamanetwork.com/journals/jama/fullarticle/2769612?fbclid=IwAR0sp9eU5V9FOzuLjz6ERw6LRFm-1yx3MJt1OEgqBDQKW1GA5mQeIIi5J7E765Please respect copyright.PENANAsbGfNDaOEj
Ref3:https://science.sciencemag.org/content/369/6499/77?fbclid=IwAR29zOO06gVsQAC2jLU2uMJi-qcYbniz108Y4kcaWOr1iNuQyVM3jCFMHa4765Please respect copyright.PENANACZcUPhav0m
Ref4:https://www.nature.com/articles/s41586-020-2538-8.pdf765Please respect copyright.PENANARCJj9r7t24
Ref5:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115629/765Please respect copyright.PENANAHdrV261Tu2