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。870Please respect copyright.PENANAlcBOn3KdVJ
870Please respect copyright.PENANA6bil3yhg2T
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。870Please respect copyright.PENANAhncbztEXW2870Please respect copyright.PENANARll3sncAGs
870Please respect copyright.PENANADlvTXGfkOG
(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。870Please respect copyright.PENANAT4wUm0rCYL
870Please respect copyright.PENANAXdqgJNkyZX
下列為Sinovac製作滅活病毒疫苗的扼要流程(Ref3)870Please respect copyright.PENANAX21YzpBQfA
870Please respect copyright.PENANAmBWxq9AsSv
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。870Please respect copyright.PENANAh9i0IB0Tya
870Please respect copyright.PENANA2LaRtV7o59
2.經過數輪實驗室細胞的培植,使病毒數量增加。870Please respect copyright.PENANA5r0OJl8thU
870Please respect copyright.PENANASqMJX3ESkq
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。870Please respect copyright.PENANAjr3p4v70uN
870Please respect copyright.PENANAX2PrZX6Kw0
4.將其製成可注射的疫苗。870Please respect copyright.PENANAhfCybYNstw
870Please respect copyright.PENANALJX0uPeoYS870Please respect copyright.PENANAnfDdaBWskH
870Please respect copyright.PENANA8Jmd5AYyhr
(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。870Please respect copyright.PENANAFMb6nIM8Tw
870Please respect copyright.PENANACOVv71lBpr
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。870Please respect copyright.PENANAiVlhKWO7iE
https://www.penana.com/article/466568870Please respect copyright.PENANAtVUninT9GS
870Please respect copyright.PENANAfvtqUgfqDb870Please respect copyright.PENANA4JJOOGTYI0
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870Please respect copyright.PENANAP7mKIJBLt4870Please respect copyright.PENANALQdI39U7YT
870Please respect copyright.PENANAlwc6lXPlum
(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。870Please respect copyright.PENANARh8ODF5CKb
870Please respect copyright.PENANArBYQImUUWn
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。870Please respect copyright.PENANAKaTldyq7iL
870Please respect copyright.PENANAE8qPYz8Yqg
1.抗體與病毒的S protein合併,870Please respect copyright.PENANAJG54eZ9jza
防止條件1的達成。870Please respect copyright.PENANAxsfoITkLS1
870Please respect copyright.PENANAKZICLFR9r7
2.抗體與病毒其他位置合併,870Please respect copyright.PENANAQ6p5WonbiE
防止條件3的達成。870Please respect copyright.PENANARl8syPYQEC
870Please respect copyright.PENANA86bannMNWC870Please respect copyright.PENANAIm8yNEozfC
870Please respect copyright.PENANA7tIBxmFqei
(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。870Please respect copyright.PENANAvtdMA2lptE
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。870Please respect copyright.PENANAG8TnJ76zNj
870Please respect copyright.PENANAE0SHd05sjr
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。870Please respect copyright.PENANAiasixbUqBD
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870Please respect copyright.PENANACPtC1kH1ra870Please respect copyright.PENANAdTczg5PzIv
870Please respect copyright.PENANAs9SNULCS9p
(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;870Please respect copyright.PENANAj4KBl2TIS5
簡單來說,就是抗體適得其反地協助病毒入侵人體細胞。870Please respect copyright.PENANAFOeZA2ONCZ
870Please respect copyright.PENANAGl6LNc7O3M
免疫細胞的表面上,有著接收器識辨抗體的某個區域。870Please respect copyright.PENANA2uge7oCsSI
870Please respect copyright.PENANAzI5aVMgKJn
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。870Please respect copyright.PENANAnm62IXTyzd
870Please respect copyright.PENANAXa3whJurGc
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。870Please respect copyright.PENANAkPfYjy7Yvo
870Please respect copyright.PENANAwhTqe73Pd3870Please respect copyright.PENANAitBR82UVKt
870Please respect copyright.PENANA7ZLeC9bYDv
(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。870Please respect copyright.PENANAgEt3Mnmw1b
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。870Please respect copyright.PENANA1lrWOMXwkf
870Please respect copyright.PENANAdV6JZp6jXI
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。870Please respect copyright.PENANAe81C4N2XMY
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。870Please respect copyright.PENANA9u5GsLzxct
870Please respect copyright.PENANAR2cuvVHhLU870Please respect copyright.PENANAMAdfbjsAyd
870Please respect copyright.PENANA9Vm7bK575A
(圖8)ADE這現象,科學家一直以來均有記錄及研究。(Ref4)870Please respect copyright.PENANAZCRgEtsH4V
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。870Please respect copyright.PENANA93oK19GnDh
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。870Please respect copyright.PENANAOaG2LsB33K
870Please respect copyright.PENANANsp4UUqdmU
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。870Please respect copyright.PENANA3tNkQVSYsi
870Please respect copyright.PENANAWzmHSgwQO0870Please respect copyright.PENANATbzbg9FsGI
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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)870Please respect copyright.PENANA7VjTL2KWSV
870Please respect copyright.PENANADDXgqrJmdK
武肺會否出現同樣現象,暫時尚未清楚。870Please respect copyright.PENANAaZXueRhR4E
870Please respect copyright.PENANA8EhyO75TOT
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。870Please respect copyright.PENANANlpTZRNpVB
870Please respect copyright.PENANAhDN4vGyIvv
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。870Please respect copyright.PENANAWD9akAqcuQ
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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!870Please respect copyright.PENANAKAJQHmjJ6o
870Please respect copyright.PENANAFBS1xqIQdn
如果想我快啲出文的話,請入去Penana網站科普專欄–薯不揀單俾一個like以及Bookmark,這對我非常之重要。870Please respect copyright.PENANArhvnXo4IhV
870Please respect copyright.PENANA38sITDtOuJ
Link: https://www.penana.com/story/66244/%E7%A7%91%E6%99%AE%E5%B0%88%E6%AC%84-%E8%96%AF%E4%B8%8D%E6%8F%80%E5%96%AE/toc870Please respect copyright.PENANAzz5j2ZuLBv
870Please respect copyright.PENANABjMV3U7dDI
同時亦可以在Penana網站裡按「買一嚿/半嚿薯仔」,以課金的方式推動我繼續搜羅資料寫文,多謝。870Please respect copyright.PENANAZ5NqAMUsSp
870Please respect copyright.PENANAxjSzjbS0JB
Link:870Please respect copyright.PENANABjZutjSqkM
https://www.penana.com/user/27349/%E8%96%AF%E4%BB%94%E8%81%9E%E8%8C%B1%E8%8E%89/portfolio870Please respect copyright.PENANAdYDUSbNquI
870Please respect copyright.PENANAUSgNCJdzzM
870Please respect copyright.PENANAzjdEEoSHQF
有興趣接收科普資訊的話,歡迎follow IG: potatopigtongue。870Please respect copyright.PENANAed4P6hLXtf
870Please respect copyright.PENANA9KrwWsRiRW
870Please respect copyright.PENANAjIjA4C9IyJ
Ref2:https://jamanetwork.com/journals/jama/fullarticle/2769612?fbclid=IwAR0sp9eU5V9FOzuLjz6ERw6LRFm-1yx3MJt1OEgqBDQKW1GA5mQeIIi5J7E870Please respect copyright.PENANAtEKBdC31Zg
Ref3:https://science.sciencemag.org/content/369/6499/77?fbclid=IwAR29zOO06gVsQAC2jLU2uMJi-qcYbniz108Y4kcaWOr1iNuQyVM3jCFMHa4870Please respect copyright.PENANAdYFvUirsuK
Ref4:https://www.nature.com/articles/s41586-020-2538-8.pdf870Please respect copyright.PENANA1Expuk3txz
Ref5:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115629/870Please respect copyright.PENANAvOChk43GdK
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科普專欄–薯不揀單
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科普專欄–薯不揀單
Author:
薯仔聞茱莉

ISSUE #23
<<深入淺出–中國兩隻臨床Phase3中疫苗的潛在反效果>>
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