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。814Please respect copyright.PENANAVh7kmVsBbl
814Please respect copyright.PENANAdbcT7PJP3z
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。814Please respect copyright.PENANAEu4KKNZrRu814Please respect copyright.PENANA5WNSuuA39H
814Please respect copyright.PENANAMrG2evjGYR
(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。814Please respect copyright.PENANAxYpnKr11cV
814Please respect copyright.PENANApDU0AAp6PL
下列為Sinovac製作滅活病毒疫苗的扼要流程(Ref3)814Please respect copyright.PENANAKNX3V5eKan
814Please respect copyright.PENANAV5bR80y0xu
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。814Please respect copyright.PENANA7cwciZAxHT
814Please respect copyright.PENANAsSDBr0Avec
2.經過數輪實驗室細胞的培植,使病毒數量增加。814Please respect copyright.PENANANLlGsKCyYH
814Please respect copyright.PENANAXOwuAxVUmH
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。814Please respect copyright.PENANAf9PDY9k9U6
814Please respect copyright.PENANAJGnlJp0xOv
4.將其製成可注射的疫苗。814Please respect copyright.PENANA9VygnL9YVL
814Please respect copyright.PENANAgFJFCHednk814Please respect copyright.PENANAB0cu5W95iZ
814Please respect copyright.PENANAXKoYERWVzH
(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。814Please respect copyright.PENANAjxXOZ82Dm5
814Please respect copyright.PENANAnIedn9cS3Y
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。814Please respect copyright.PENANA7yu4XDna2C
https://www.penana.com/article/466568814Please respect copyright.PENANAQR0bFnVZkG
814Please respect copyright.PENANAKL3VNuOaJi814Please respect copyright.PENANA2RjBh3OC2m
814Please respect copyright.PENANAN86GJCvCjp
814Please respect copyright.PENANAudZrRBLoEK
814Please respect copyright.PENANAuYT2nDSL7a
814Please respect copyright.PENANAWkUCHA6m99814Please respect copyright.PENANAy0jPHynGam
814Please respect copyright.PENANAUwCxAUidyo
(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。814Please respect copyright.PENANAqOPibtlXxE
814Please respect copyright.PENANAfmH2qORPqw
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。814Please respect copyright.PENANA2rZkM4LmZS
814Please respect copyright.PENANAZLGygl0TXf
1.抗體與病毒的S protein合併,814Please respect copyright.PENANA1jHi4UpVtx
防止條件1的達成。814Please respect copyright.PENANA0AC54UilBp
814Please respect copyright.PENANAaIRpSUkIOC
2.抗體與病毒其他位置合併,814Please respect copyright.PENANAyHwC8zcdJV
防止條件3的達成。814Please respect copyright.PENANAZx8V1B2puy
814Please respect copyright.PENANARA81bWQvyJ814Please respect copyright.PENANAAyMGUunmSm
814Please respect copyright.PENANAKM2KQmusAZ
(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。814Please respect copyright.PENANA3qcaEIMtH6
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。814Please respect copyright.PENANApxk1JJjMqh
814Please respect copyright.PENANAuJY5DaVACD
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。814Please respect copyright.PENANA5Z0v4NTXxK
814Please respect copyright.PENANAwv6YxELxhQ
814Please respect copyright.PENANAYWuo1mQFkk814Please respect copyright.PENANAIsiOxasAMo
814Please respect copyright.PENANApBJKySSPub
(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;814Please respect copyright.PENANAyYy0NcWSid
簡單來說,就是抗體適得其反地協助病毒入侵人體細胞。814Please respect copyright.PENANAErKZpnydNF
814Please respect copyright.PENANAytExFMOQMb
免疫細胞的表面上,有著接收器識辨抗體的某個區域。814Please respect copyright.PENANAZHAdHcZSIa
814Please respect copyright.PENANAm4MqtCca5L
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。814Please respect copyright.PENANAoBpFT2iAw8
814Please respect copyright.PENANAsQYGWK0iAm
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。814Please respect copyright.PENANASxZ9YsE3N9
814Please respect copyright.PENANAkH6u0SNng4814Please respect copyright.PENANAF28JuxfZmH
814Please respect copyright.PENANAnxO31LQR7C
(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。814Please respect copyright.PENANAfjg07TU5Yq
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。814Please respect copyright.PENANAvappFnvtMO
814Please respect copyright.PENANAvnlO4CAaFF
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。814Please respect copyright.PENANAvbeSlBiMiB
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。814Please respect copyright.PENANAYePN4jOcrD
814Please respect copyright.PENANASYR6tQNqSJ814Please respect copyright.PENANAmsKN74OVZv
814Please respect copyright.PENANASaqZQq7bSB
(圖8)ADE這現象,科學家一直以來均有記錄及研究。(Ref4)814Please respect copyright.PENANAMADxybiYev
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。814Please respect copyright.PENANAOlZwxbfH4j
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。814Please respect copyright.PENANA7sFGXNT7bR
814Please respect copyright.PENANAZdEEh4KjXd
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。814Please respect copyright.PENANA6XlwxFyezk
814Please respect copyright.PENANAUcBUE15IPx814Please respect copyright.PENANAtgf5schfN3
814Please respect copyright.PENANAQK9nhPz9Tt
(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)814Please respect copyright.PENANATbA0rRgxC3
814Please respect copyright.PENANA9w9CESW0al
武肺會否出現同樣現象,暫時尚未清楚。814Please respect copyright.PENANA22WcGDUjlf
814Please respect copyright.PENANAD2dXypqztq
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。814Please respect copyright.PENANAawQ8yUCORM
814Please respect copyright.PENANApqCV3Nw6Vv
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。814Please respect copyright.PENANAtb8xtOGoDx
814Please respect copyright.PENANAYgN5AYnhcl
814Please respect copyright.PENANAd1yiL2Oy34
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!814Please respect copyright.PENANAtMq7vykpTQ
814Please respect copyright.PENANApvHvfukkQw
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。814Please respect copyright.PENANALZe3Il08Ro
814Please respect copyright.PENANAGZnmXqJO7I
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/toc814Please respect copyright.PENANA4mcE5GRxoI
814Please respect copyright.PENANAumc0ZUWw2d
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。814Please respect copyright.PENANAB9mEhDYcIw
814Please respect copyright.PENANAPhCUOeRUAI
Link:814Please respect copyright.PENANArSulVoNwJK
https://www.penana.com/user/27349/%E8%96%AF%E4%BB%94%E8%81%9E%E8%8C%B1%E8%8E%89/portfolio814Please respect copyright.PENANARjGFsC6Tt1
814Please respect copyright.PENANAU4wIQvuPfY
814Please respect copyright.PENANAcKBDDvc1ye
有興趣接收科普資訊的話,歡迎follow IG: potatopigtongue。814Please respect copyright.PENANAh36PSA0XLQ
814Please respect copyright.PENANAoLzyAshhaT
814Please respect copyright.PENANA6xqFrdM4ci
Ref2:https://jamanetwork.com/journals/jama/fullarticle/2769612?fbclid=IwAR0sp9eU5V9FOzuLjz6ERw6LRFm-1yx3MJt1OEgqBDQKW1GA5mQeIIi5J7E814Please respect copyright.PENANAeaWb5DXNno
Ref3:https://science.sciencemag.org/content/369/6499/77?fbclid=IwAR29zOO06gVsQAC2jLU2uMJi-qcYbniz108Y4kcaWOr1iNuQyVM3jCFMHa4814Please respect copyright.PENANAFI9nCWjsF9
Ref4:https://www.nature.com/articles/s41586-020-2538-8.pdf814Please respect copyright.PENANAIkPFwqAEVP
Ref5:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115629/814Please respect copyright.PENANAjlE4T4jSBs