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。610Please respect copyright.PENANAIkiMnMqKs2
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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。610Please respect copyright.PENANAfVqEwyV616
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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。610Please respect copyright.PENANAGecsjz2N7C
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下列為Sinovac製作滅活病毒疫苗的扼要流程(Ref3)610Please respect copyright.PENANAhkB8pJKFe8
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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。610Please respect copyright.PENANA2D68Vs2U9C
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2.經過數輪實驗室細胞的培植,使病毒數量增加。610Please respect copyright.PENANATnFat8ug18
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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。610Please respect copyright.PENANAWYNB0voo2d
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4.將其製成可注射的疫苗。610Please respect copyright.PENANAHTveRMSgTF
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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。610Please respect copyright.PENANAwdDc1gRIvk
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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。610Please respect copyright.PENANADNGj8uf0WQ
https://www.penana.com/article/466568610Please respect copyright.PENANAgrc86PLP8i
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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。610Please respect copyright.PENANA0eNUGkFIGP
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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。610Please respect copyright.PENANASPOt3R2JEJ
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1.抗體與病毒的S protein合併,610Please respect copyright.PENANA6AYcnbH6jq
防止條件1的達成。610Please respect copyright.PENANAX9DxFO5CzE
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2.抗體與病毒其他位置合併,610Please respect copyright.PENANAoKJYFA8D3H
防止條件3的達成。610Please respect copyright.PENANAS9xZsWZJVi
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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。610Please respect copyright.PENANA7hKXEtK3kD
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。610Please respect copyright.PENANAnDfjxkoWee
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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。610Please respect copyright.PENANAe0lS8edLQL
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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;610Please respect copyright.PENANApzDE6SHEFu
簡單來說,就是抗體適得其反地協助病毒入侵人體細胞。610Please respect copyright.PENANAkENT5bHOTx
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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。610Please respect copyright.PENANAoMDKYdHf5a
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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。610Please respect copyright.PENANA5bwgDbo85h
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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。610Please respect copyright.PENANAp7lSbqOkvU
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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。610Please respect copyright.PENANAbCxbUL3ugy
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。610Please respect copyright.PENANAI6PwnFYL6Q
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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。610Please respect copyright.PENANAq901qaJ5wO
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。610Please respect copyright.PENANAfApNGG5eSy
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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)610Please respect copyright.PENANA4MuPG29XH0
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。610Please respect copyright.PENANAGmINF1bZRk
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。610Please respect copyright.PENANAaFCULiBsph
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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。610Please respect copyright.PENANAeJxusFUNUw
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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)610Please respect copyright.PENANAUKrU08Ah7r
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武肺會否出現同樣現象,暫時尚未清楚。610Please respect copyright.PENANANsupq0RszY
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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。610Please respect copyright.PENANAQQXcAyFQ8B
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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。610Please respect copyright.PENANAWk865lReWa
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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!610Please respect copyright.PENANAQioJbIz2Do
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Ref2:https://jamanetwork.com/journals/jama/fullarticle/2769612?fbclid=IwAR0sp9eU5V9FOzuLjz6ERw6LRFm-1yx3MJt1OEgqBDQKW1GA5mQeIIi5J7E610Please respect copyright.PENANAv0oNn6nvGA
Ref3:https://science.sciencemag.org/content/369/6499/77?fbclid=IwAR29zOO06gVsQAC2jLU2uMJi-qcYbniz108Y4kcaWOr1iNuQyVM3jCFMHa4610Please respect copyright.PENANAMBiOFdwdEV
Ref4:https://www.nature.com/articles/s41586-020-2538-8.pdf610Please respect copyright.PENANAE7OpJlWirX
Ref5:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115629/610Please respect copyright.PENANAci2LYweuFW