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。791Please respect copyright.PENANAZnyzVRY7W0
791Please respect copyright.PENANAUNvPqnC5p9
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。791Please respect copyright.PENANA4vLZH3Bn9G791Please respect copyright.PENANASbr6gwiHK6
791Please respect copyright.PENANACNjhDKmDBu
(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。791Please respect copyright.PENANADUGcNmS3TH
791Please respect copyright.PENANAj4UyrRwNTU
下列為Sinovac製作滅活病毒疫苗的扼要流程(Ref3)791Please respect copyright.PENANAasDtM21avz
791Please respect copyright.PENANAlAS8qB7itw
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。791Please respect copyright.PENANAUCFKfwEMdD
791Please respect copyright.PENANAyy0rlBeijD
2.經過數輪實驗室細胞的培植,使病毒數量增加。791Please respect copyright.PENANAgPIUlUwHOs
791Please respect copyright.PENANACTj1PlfnyN
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。791Please respect copyright.PENANAdvimexSE8r
791Please respect copyright.PENANANdg0kd4GWT
4.將其製成可注射的疫苗。791Please respect copyright.PENANAWBSqRnwxVY
791Please respect copyright.PENANAbVe6S7tfav791Please respect copyright.PENANAGJY59K73tn
791Please respect copyright.PENANAsSBL5PyiiK
(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。791Please respect copyright.PENANAduZU9f76Xy
791Please respect copyright.PENANAKMsYrEmXAT
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。791Please respect copyright.PENANAonjNb6YmPa
https://www.penana.com/article/466568791Please respect copyright.PENANAecIJjo9ucZ
791Please respect copyright.PENANA4RqvihbBCY791Please respect copyright.PENANAaxGpJb7tfV
791Please respect copyright.PENANAzgdX8AiMkS
791Please respect copyright.PENANAwpHtIgeWEk
791Please respect copyright.PENANAH42GHqKsrk
791Please respect copyright.PENANA9A3FPePXkS791Please respect copyright.PENANAef4UF5sV8s
791Please respect copyright.PENANAy4S457vCMD
(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。791Please respect copyright.PENANAe9tzyS3HEb
791Please respect copyright.PENANApKaffDl3wJ
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。791Please respect copyright.PENANAJwbW6nnI6h
791Please respect copyright.PENANA7jtj3UU44H
1.抗體與病毒的S protein合併,791Please respect copyright.PENANAZDa8w08Dt6
防止條件1的達成。791Please respect copyright.PENANABrUFZioUgc
791Please respect copyright.PENANAM8XQmTtUJp
2.抗體與病毒其他位置合併,791Please respect copyright.PENANAHokvkNoq6S
防止條件3的達成。791Please respect copyright.PENANA5GvTYvR2SJ
791Please respect copyright.PENANA1aAuqFA7TE791Please respect copyright.PENANA9g1QJM2rP6
791Please respect copyright.PENANAbRlQxvL9gW
(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。791Please respect copyright.PENANAatZAJ2i0GS
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。791Please respect copyright.PENANAHJov6khPQu
791Please respect copyright.PENANAjPxwKyG9wI
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。791Please respect copyright.PENANAvZl8r6G9Md
791Please respect copyright.PENANAH3pDKncZvQ
791Please respect copyright.PENANAPpf0ez3fvt791Please respect copyright.PENANAQh0zjMlqWM
791Please respect copyright.PENANAi0pBOcxiQz
(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;791Please respect copyright.PENANAkRBJdXRv2o
簡單來說,就是抗體適得其反地協助病毒入侵人體細胞。791Please respect copyright.PENANA9gFiHiEzLF
791Please respect copyright.PENANANTH0x971tK
免疫細胞的表面上,有著接收器識辨抗體的某個區域。791Please respect copyright.PENANAMWOCEjTuCX
791Please respect copyright.PENANA2e83MZzHip
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。791Please respect copyright.PENANABo0aTj4mkS
791Please respect copyright.PENANAQnaDxZkPNk
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。791Please respect copyright.PENANATtmqrygiQl
791Please respect copyright.PENANA8JP8eFP7LG791Please respect copyright.PENANAepYvr11Seu
791Please respect copyright.PENANA3OIBpsHzYv
(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。791Please respect copyright.PENANAu4BNlEgB4l
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。791Please respect copyright.PENANAld31PhednT
791Please respect copyright.PENANAeDmX7YFvDQ
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。791Please respect copyright.PENANAvx5BcxFYyD
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。791Please respect copyright.PENANAE6COSj2Bi5
791Please respect copyright.PENANAthsaflUfDT791Please respect copyright.PENANA52TdqOhcpj
791Please respect copyright.PENANAVpK7gL9RSk
(圖8)ADE這現象,科學家一直以來均有記錄及研究。(Ref4)791Please respect copyright.PENANArNKXPDViFK
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。791Please respect copyright.PENANAfKWJOMJoCD
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。791Please respect copyright.PENANAq00ProIeUQ
791Please respect copyright.PENANAifY943Hc0u
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。791Please respect copyright.PENANA6vBeqzMtVc
791Please respect copyright.PENANAFCMkJjcc1p791Please respect copyright.PENANAIZX9hPTA7H
791Please respect copyright.PENANAmf0F3SJEaN
(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)791Please respect copyright.PENANAjvU60nl5L6
791Please respect copyright.PENANA3pmhCJmQEJ
武肺會否出現同樣現象,暫時尚未清楚。791Please respect copyright.PENANAoblNEcaDB2
791Please respect copyright.PENANAmyAI54LEq1
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。791Please respect copyright.PENANA4CegWSN3Hx
791Please respect copyright.PENANAFJ1QPY6rgz
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。791Please respect copyright.PENANA9AlJfYsrpS
791Please respect copyright.PENANAmodmhxx2Ke
791Please respect copyright.PENANADPO58WRS6o
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!791Please respect copyright.PENANAocsnPg9qFP
791Please respect copyright.PENANAAGnk7r453C
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。791Please respect copyright.PENANAN3ng9kn4Gu
791Please respect copyright.PENANA5pcna4LND0
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/toc791Please respect copyright.PENANA7Hx645sb1P
791Please respect copyright.PENANAI77i4TgkJ1
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。791Please respect copyright.PENANAa2xQKS1JGV
791Please respect copyright.PENANAHl33fWU88P
Link:791Please respect copyright.PENANA7xRD6i3sHw
https://www.penana.com/user/27349/%E8%96%AF%E4%BB%94%E8%81%9E%E8%8C%B1%E8%8E%89/portfolio791Please respect copyright.PENANAP67ZTkSCpL
791Please respect copyright.PENANApPH0ncTP4R
791Please respect copyright.PENANAxxSk5gQGgO
有興趣接收科普資訊的話,歡迎follow IG: potatopigtongue。791Please respect copyright.PENANA35EpasGXB9
791Please respect copyright.PENANAio07A7BHPt
791Please respect copyright.PENANAbTLYfS2YUb
Ref2:https://jamanetwork.com/journals/jama/fullarticle/2769612?fbclid=IwAR0sp9eU5V9FOzuLjz6ERw6LRFm-1yx3MJt1OEgqBDQKW1GA5mQeIIi5J7E791Please respect copyright.PENANABE1Mar1s2i
Ref3:https://science.sciencemag.org/content/369/6499/77?fbclid=IwAR29zOO06gVsQAC2jLU2uMJi-qcYbniz108Y4kcaWOr1iNuQyVM3jCFMHa4791Please respect copyright.PENANAqZ6gf7HWEf
Ref4:https://www.nature.com/articles/s41586-020-2538-8.pdf791Please respect copyright.PENANAp4nqlMpLX1
Ref5:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115629/791Please respect copyright.PENANAGHnKqZT19y