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。869Please respect copyright.PENANAtBaFjuYvxp
869Please respect copyright.PENANAWNZ0b2MXYE
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。869Please respect copyright.PENANAqB7cLgHtpq869Please respect copyright.PENANA61KaeNR0B7
869Please respect copyright.PENANAZgZJLHZeGS
(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。869Please respect copyright.PENANAGwFCPc0JyP
869Please respect copyright.PENANASXgWcSlGCY
下列為Sinovac製作滅活病毒疫苗的扼要流程(Ref3)869Please respect copyright.PENANAgRZuwpvBHr
869Please respect copyright.PENANAMtqoGoCeKq
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。869Please respect copyright.PENANA8YRqMofWQ0
869Please respect copyright.PENANAZXNKVp0GhL
2.經過數輪實驗室細胞的培植,使病毒數量增加。869Please respect copyright.PENANAA7Zd4raMoa
869Please respect copyright.PENANAjTBkC0pWeU
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。869Please respect copyright.PENANASaQ30eqTkA
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4.將其製成可注射的疫苗。869Please respect copyright.PENANAWz5pxv45f5
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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。869Please respect copyright.PENANA90bT3xyAJI
869Please respect copyright.PENANAaAihkwzREj
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。869Please respect copyright.PENANA9YE2LLi8Wo
https://www.penana.com/article/466568869Please respect copyright.PENANAdW2HoCVZ3S
869Please respect copyright.PENANAMq3X2TNaS7869Please respect copyright.PENANAPyHMQiBKma
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869Please respect copyright.PENANA19NPPcanlu869Please respect copyright.PENANAwtT0iHW9gi
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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。869Please respect copyright.PENANAnvaE4Luntr
869Please respect copyright.PENANAzn5vl8Vy3G
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。869Please respect copyright.PENANAJFxcjN5vjv
869Please respect copyright.PENANAyNdOphwqGf
1.抗體與病毒的S protein合併,869Please respect copyright.PENANAQVdHuf58jb
防止條件1的達成。869Please respect copyright.PENANAfAD85rfj23
869Please respect copyright.PENANAqhCXVV2TFu
2.抗體與病毒其他位置合併,869Please respect copyright.PENANAR9Kcx4fpC8
防止條件3的達成。869Please respect copyright.PENANAn0SiSOzcqI
869Please respect copyright.PENANAmVaOG7FREI869Please respect copyright.PENANATLeO68wzPg
869Please respect copyright.PENANA0OM83VYW5e
(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。869Please respect copyright.PENANAK1RG2AAYvF
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。869Please respect copyright.PENANAM2p45Vu3zq
869Please respect copyright.PENANACUan6jlRqb
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。869Please respect copyright.PENANAY2Neyo9SZu
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869Please respect copyright.PENANAFFkbRNqV6V869Please respect copyright.PENANAgCuYBxVihH
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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;869Please respect copyright.PENANAbSpgRTw08B
簡單來說,就是抗體適得其反地協助病毒入侵人體細胞。869Please respect copyright.PENANA1wW5gjERx1
869Please respect copyright.PENANAPT4GlAEOk6
免疫細胞的表面上,有著接收器識辨抗體的某個區域。869Please respect copyright.PENANA1uIXALHyLZ
869Please respect copyright.PENANAxvGvln8v1q
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。869Please respect copyright.PENANAvRGNSlaY14
869Please respect copyright.PENANAJ5RsTgqeRt
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。869Please respect copyright.PENANABbYY0KLpyv
869Please respect copyright.PENANAe3k5kBHlka869Please respect copyright.PENANABQHscXEkos
869Please respect copyright.PENANA1lpFttv8Ug
(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。869Please respect copyright.PENANAwgKGygA7p1
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。869Please respect copyright.PENANA9R0cVi7mrg
869Please respect copyright.PENANAHinsOoLo2i
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。869Please respect copyright.PENANAkJJhrNREgd
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。869Please respect copyright.PENANAsPxlWWM57Z
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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)869Please respect copyright.PENANAb8FAFvzTbq
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。869Please respect copyright.PENANAd4feLKw5KY
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。869Please respect copyright.PENANAOLVvQ03MBf
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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。869Please respect copyright.PENANAZfD0NIvKM6
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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)869Please respect copyright.PENANAmGb9rVTeQn
869Please respect copyright.PENANAaSBID3teM8
武肺會否出現同樣現象,暫時尚未清楚。869Please respect copyright.PENANA9KJFQU9gon
869Please respect copyright.PENANAPG9a6PYA7A
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。869Please respect copyright.PENANANO9zAvJzGw
869Please respect copyright.PENANAw2WoH9HMvM
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。869Please respect copyright.PENANA9i1mS3SZFg
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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!869Please respect copyright.PENANAF8y4tAsxJt
869Please respect copyright.PENANA8aXzUNixgU
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。869Please respect copyright.PENANAgsqnzEsBL9
869Please respect copyright.PENANAJmHDlTPXtl
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/toc869Please respect copyright.PENANADp5Bu2mGUl
869Please respect copyright.PENANACH50wS1TJm
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。869Please respect copyright.PENANAb7MX1lotRD
869Please respect copyright.PENANAWsZ3EPF3Bx
Link:869Please respect copyright.PENANAyBPyPNxFyW
https://www.penana.com/user/27349/%E8%96%AF%E4%BB%94%E8%81%9E%E8%8C%B1%E8%8E%89/portfolio869Please respect copyright.PENANA17E871j0Er
869Please respect copyright.PENANAQ46LZonGci
869Please respect copyright.PENANAug7Yvr8pkv
有興趣接收科普資訊的話,歡迎follow IG: potatopigtongue。869Please respect copyright.PENANAgTvBhmVeZw
869Please respect copyright.PENANA3SxB21wHed
869Please respect copyright.PENANAvFXgglGO4x
Ref2:https://jamanetwork.com/journals/jama/fullarticle/2769612?fbclid=IwAR0sp9eU5V9FOzuLjz6ERw6LRFm-1yx3MJt1OEgqBDQKW1GA5mQeIIi5J7E869Please respect copyright.PENANAm3jnKafuN6
Ref3:https://science.sciencemag.org/content/369/6499/77?fbclid=IwAR29zOO06gVsQAC2jLU2uMJi-qcYbniz108Y4kcaWOr1iNuQyVM3jCFMHa4869Please respect copyright.PENANAxv6x1daP1P
Ref4:https://www.nature.com/articles/s41586-020-2538-8.pdf869Please respect copyright.PENANAqjtlVqszjA
Ref5:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115629/869Please respect copyright.PENANAIJ5CgEka7l
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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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