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。686Please respect copyright.PENANAPOl1hEv0rU
686Please respect copyright.PENANAcnO59n7l5e
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。686Please respect copyright.PENANA9NvsSl91CP
686Please respect copyright.PENANAxUcniJej7P
686Please respect copyright.PENANASbAXxiswaK
(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。686Please respect copyright.PENANAIen3jGK5g0
686Please respect copyright.PENANAC7I2w2UGH5
下列為Sinovac製作滅活病毒疫苗的扼要流程(Ref3)686Please respect copyright.PENANA4Kb7oQrjpg
686Please respect copyright.PENANAb27iEGdR1H
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。686Please respect copyright.PENANAFmLBcRlFk2
686Please respect copyright.PENANANPoQZG3oqG
2.經過數輪實驗室細胞的培植,使病毒數量增加。686Please respect copyright.PENANAuVm0EjLAeD
686Please respect copyright.PENANAMFTE8lWNox
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。686Please respect copyright.PENANA8N6HiU2833
686Please respect copyright.PENANA4cYS8vZlBM
4.將其製成可注射的疫苗。686Please respect copyright.PENANAKhlA7DTAeg
686Please respect copyright.PENANAaPTBpphimG
686Please respect copyright.PENANAls8jN3dRzz
686Please respect copyright.PENANALl9gi0BFR0
(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。686Please respect copyright.PENANAeSxWeFO4rM
686Please respect copyright.PENANAYIQ39dVhbU
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。686Please respect copyright.PENANAkXw4PbUnrg
https://www.penana.com/article/466568686Please respect copyright.PENANAj4PWzEusQM
686Please respect copyright.PENANAqIawErjtLu
686Please respect copyright.PENANAstABxuvgWW
686Please respect copyright.PENANAdpe440CGPW
686Please respect copyright.PENANATaCtYd9OBk
686Please respect copyright.PENANAV18seLGKFY
686Please respect copyright.PENANAER1jXjhZrn
686Please respect copyright.PENANAONnTmXOsfO
686Please respect copyright.PENANAs3V7zEfAYT
(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。686Please respect copyright.PENANA5NR8giUVto
686Please respect copyright.PENANA5SkGRdygbp
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。686Please respect copyright.PENANAgLsLXjW5Hh
686Please respect copyright.PENANAb8vYDIXjjq
1.抗體與病毒的S protein合併,686Please respect copyright.PENANAXKdZLmhLlo
防止條件1的達成。686Please respect copyright.PENANAQ0al1TVNlT
686Please respect copyright.PENANAspPp7XZG7u
2.抗體與病毒其他位置合併,686Please respect copyright.PENANAJNXCVil8Ji
防止條件3的達成。686Please respect copyright.PENANAjEIJLVyTUR
686Please respect copyright.PENANAE50w6Po86Z
686Please respect copyright.PENANAH5k2wuGDSC
686Please respect copyright.PENANAt2BRRUFquY
(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。686Please respect copyright.PENANAwrEOkvlQ86
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。686Please respect copyright.PENANAz1h06ehZTB
686Please respect copyright.PENANAQayLDtOrio
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。686Please respect copyright.PENANAuMDKCJ1EB6
686Please respect copyright.PENANA5TAV4Z4c8a
686Please respect copyright.PENANALZCKO2RIoE
686Please respect copyright.PENANAUEYFxwH5aX
686Please respect copyright.PENANAoxcgtbFVoA
(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;686Please respect copyright.PENANA5xDtvgezVS
簡單來說,就是抗體適得其反地協助病毒入侵人體細胞。686Please respect copyright.PENANASEUNBqYoJa
686Please respect copyright.PENANApQxFTGWWu5
免疫細胞的表面上,有著接收器識辨抗體的某個區域。686Please respect copyright.PENANAkPnfFCOxIG
686Please respect copyright.PENANAqaPnVUUYKK
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。686Please respect copyright.PENANASkmklolxjc
686Please respect copyright.PENANA8fBN8cE3Ly
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。686Please respect copyright.PENANAtKJqe2FM06
686Please respect copyright.PENANAWGQ6BxYxKJ
686Please respect copyright.PENANAzIwtm12tFj
686Please respect copyright.PENANAQrhp4rWUQr
(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。686Please respect copyright.PENANAIjUSCAMhTE
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。686Please respect copyright.PENANAAMzo7Os3il
686Please respect copyright.PENANAo3oCrFLiUO
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。686Please respect copyright.PENANADl2KVfy4mS
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。686Please respect copyright.PENANA8BqLBIS4SC
686Please respect copyright.PENANALDnx0RVsdp
686Please respect copyright.PENANAUXe0NpC7Ej
686Please respect copyright.PENANALtW6ehnbHJ
(圖8)ADE這現象,科學家一直以來均有記錄及研究。(Ref4)686Please respect copyright.PENANA9DK0CWpISC
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。686Please respect copyright.PENANA3vfgHTTwVR
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。686Please respect copyright.PENANAOAhwCu50w4
686Please respect copyright.PENANA5QbOD6I2D9
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。686Please respect copyright.PENANA51GLlktyPl
686Please respect copyright.PENANA9ChU8v3nk1
686Please respect copyright.PENANAFArT2NmM8D
686Please respect copyright.PENANAD0zgvhnsE9
(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)686Please respect copyright.PENANAvtIoJdPrbt
686Please respect copyright.PENANA8pQUpwGsua
武肺會否出現同樣現象,暫時尚未清楚。686Please respect copyright.PENANAxoLotEwALN
686Please respect copyright.PENANAWKVnUVA4mU
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。686Please respect copyright.PENANANr5A53SxaB
686Please respect copyright.PENANAJaNqRjvUf9
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。686Please respect copyright.PENANA8xfsFR4HOv
686Please respect copyright.PENANARI1s50OYiG
686Please respect copyright.PENANAKmg3c2lhEC
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!686Please respect copyright.PENANApWhRBL6wXh
686Please respect copyright.PENANA0OgQEO2q2r
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。686Please respect copyright.PENANAxX0RsxbXqA
686Please respect copyright.PENANAxNUOOvR2XO
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/toc686Please respect copyright.PENANAoSkrGhKngO
686Please respect copyright.PENANAhfuYWVv0Yh
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。686Please respect copyright.PENANAXWiCeqFpJP
686Please respect copyright.PENANA62hnRYUVp0
Link:686Please respect copyright.PENANAHX86nICYNv
https://www.penana.com/user/27349/%E8%96%AF%E4%BB%94%E8%81%9E%E8%8C%B1%E8%8E%89/portfolio686Please respect copyright.PENANArHzvTZFfXC
686Please respect copyright.PENANAETtOGmfXw0
686Please respect copyright.PENANAJDqG7RCjku
有興趣接收科普資訊的話,歡迎follow IG: potatopigtongue。686Please respect copyright.PENANAYINh82jd5e
686Please respect copyright.PENANAP0NJi7tY4n
686Please respect copyright.PENANAHw8g2tdZvN
Ref2:https://jamanetwork.com/journals/jama/fullarticle/2769612?fbclid=IwAR0sp9eU5V9FOzuLjz6ERw6LRFm-1yx3MJt1OEgqBDQKW1GA5mQeIIi5J7E686Please respect copyright.PENANATY6OWx7xsW
Ref3:https://science.sciencemag.org/content/369/6499/77?fbclid=IwAR29zOO06gVsQAC2jLU2uMJi-qcYbniz108Y4kcaWOr1iNuQyVM3jCFMHa4686Please respect copyright.PENANASDNzh12qJf
Ref4:https://www.nature.com/articles/s41586-020-2538-8.pdf686Please respect copyright.PENANACTXQN0oTLF
Ref5:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115629/686Please respect copyright.PENANAQRNTVZX6z6