科普專欄–薯不揀單 - <<深入淺出–中國兩隻臨床Phase3中疫苗的潛在反效果>>

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。822Please respect copyright.ＰＥＮＡＮＡUnVabPtYPR
822Please respect copyright.ＰＥＮＡＮＡOlWk5VyNTa
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。822Please respect copyright.ＰＥＮＡＮＡ0ebxwE2gM3
822Please respect copyright.ＰＥＮＡＮＡhNvFTyFWPA
822Please respect copyright.ＰＥＮＡＮＡR6E6PhqGaH
（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。822Please respect copyright.ＰＥＮＡＮＡUeb0wTZX00
822Please respect copyright.ＰＥＮＡＮＡ4V8WFjzkjQ
下列為Sinovac製作滅活病毒疫苗的扼要流程(Ref3)822Please respect copyright.ＰＥＮＡＮＡqy6squweHN
822Please respect copyright.ＰＥＮＡＮＡh7S18RvtHF
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。822Please respect copyright.ＰＥＮＡＮＡw3GQtcuxoe
822Please respect copyright.ＰＥＮＡＮＡBbHgGBBj5H
2.經過數輪實驗室細胞的培植，使病毒數量增加。822Please respect copyright.ＰＥＮＡＮＡWjyzvVIsto
822Please respect copyright.ＰＥＮＡＮＡNp0vfXH2Su
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。822Please respect copyright.ＰＥＮＡＮＡ9RwklhNE6F
822Please respect copyright.ＰＥＮＡＮＡLJgACd0JLg
4.將其製成可注射的疫苗。822Please respect copyright.ＰＥＮＡＮＡwQqzqLu3Y1
822Please respect copyright.ＰＥＮＡＮＡpkfbCK4aHy
822Please respect copyright.ＰＥＮＡＮＡT9JNd03nm8
822Please respect copyright.ＰＥＮＡＮＡJZ8nNo1MhN
（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。822Please respect copyright.ＰＥＮＡＮＡ7FXhmeDcv0
822Please respect copyright.ＰＥＮＡＮＡIgc1StjF5I
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。822Please respect copyright.ＰＥＮＡＮＡkhMJnMr8Gp
https://www.penana.com/article/466568822Please respect copyright.ＰＥＮＡＮＡylrAdoEffx
822Please respect copyright.ＰＥＮＡＮＡuu3ksesbLo
822Please respect copyright.ＰＥＮＡＮＡJl8dv5oKkM
822Please respect copyright.ＰＥＮＡＮＡngqK13pwM3
822Please respect copyright.ＰＥＮＡＮＡnwe356Xuno
822Please respect copyright.ＰＥＮＡＮＡvWc3w0x4JN
822Please respect copyright.ＰＥＮＡＮＡEpz5jyAoc2
822Please respect copyright.ＰＥＮＡＮＡhHjSgeRNCd
822Please respect copyright.ＰＥＮＡＮＡQXsErS0tgy
（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。822Please respect copyright.ＰＥＮＡＮＡNIvDollT8Z
822Please respect copyright.ＰＥＮＡＮＡt2ra4C9qb8
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。822Please respect copyright.ＰＥＮＡＮＡzIISPsZA0d
822Please respect copyright.ＰＥＮＡＮＡcJy1rvEh7f
1.抗體與病毒的S protein合併，822Please respect copyright.ＰＥＮＡＮＡJ2YsXGbfR3
防止條件1的達成。822Please respect copyright.ＰＥＮＡＮＡGxL4mgNsn9
822Please respect copyright.ＰＥＮＡＮＡjZT3PF5WNb
2.抗體與病毒其他位置合併，822Please respect copyright.ＰＥＮＡＮＡOLbRtcYCv0
防止條件3的達成。822Please respect copyright.ＰＥＮＡＮＡj2rb3xeO1I
822Please respect copyright.ＰＥＮＡＮＡyCDa4oHzEU
822Please respect copyright.ＰＥＮＡＮＡClVPypHHkX
822Please respect copyright.ＰＥＮＡＮＡqi6FpxFsTA
（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。822Please respect copyright.ＰＥＮＡＮＡPhUSrq1tJd
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。822Please respect copyright.ＰＥＮＡＮＡzg7XDjaBG6
822Please respect copyright.ＰＥＮＡＮＡ7DbCmx59F9
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。822Please respect copyright.ＰＥＮＡＮＡlGGQqhwnt6
822Please respect copyright.ＰＥＮＡＮＡCymAB5dvrx
822Please respect copyright.ＰＥＮＡＮＡav1m1K3CGO
822Please respect copyright.ＰＥＮＡＮＡWz3dIZMkps
822Please respect copyright.ＰＥＮＡＮＡnZNZYTBFWn
（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;822Please respect copyright.ＰＥＮＡＮＡSSTFbziVMb
簡單來說，就是抗體適得其反地協助病毒入侵人體細胞。822Please respect copyright.ＰＥＮＡＮＡMandMpquLE
822Please respect copyright.ＰＥＮＡＮＡ6qprEtR2GG
免疫細胞的表面上，有著接收器識辨抗體的某個區域。822Please respect copyright.ＰＥＮＡＮＡ6yAgoG3UMa
822Please respect copyright.ＰＥＮＡＮＡUe635DHtZa
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。822Please respect copyright.ＰＥＮＡＮＡiaieaZ9ZeX
822Please respect copyright.ＰＥＮＡＮＡjFczYF4rvn
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。822Please respect copyright.ＰＥＮＡＮＡRWN6DDQnWE
822Please respect copyright.ＰＥＮＡＮＡgdTIENnBxy
822Please respect copyright.ＰＥＮＡＮＡZiDwknlC2u
822Please respect copyright.ＰＥＮＡＮＡ5W1P9piNIH
（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。822Please respect copyright.ＰＥＮＡＮＡQJyXo1HNHW
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。822Please respect copyright.ＰＥＮＡＮＡgVAdNHmdCV
822Please respect copyright.ＰＥＮＡＮＡvGm2uHos7c
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。822Please respect copyright.ＰＥＮＡＮＡnO5Jx6v3F8
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。822Please respect copyright.ＰＥＮＡＮＡKKVQcJJnV6
822Please respect copyright.ＰＥＮＡＮＡQAffKUh7dI
822Please respect copyright.ＰＥＮＡＮＡ3XXO7u73f1
822Please respect copyright.ＰＥＮＡＮＡrSVu05SFPk
（圖8）ADE這現象，科學家一直以來均有記錄及研究。（Ref4)822Please respect copyright.ＰＥＮＡＮＡ0GHb9L9KUB
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。822Please respect copyright.ＰＥＮＡＮＡJioRpm8FB8
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。822Please respect copyright.ＰＥＮＡＮＡShHKkTsKcS
822Please respect copyright.ＰＥＮＡＮＡ8naEkZmTnn
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。822Please respect copyright.ＰＥＮＡＮＡjVHWUO2ofY
822Please respect copyright.ＰＥＮＡＮＡvHsrwFNzAj
822Please respect copyright.ＰＥＮＡＮＡT4xVWXo6B0
822Please respect copyright.ＰＥＮＡＮＡxiMdl9MZeV
（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)822Please respect copyright.ＰＥＮＡＮＡPkqflHfSJa
822Please respect copyright.ＰＥＮＡＮＡ4df8AchYt2
武肺會否出現同樣現象，暫時尚未清楚。822Please respect copyright.ＰＥＮＡＮＡ78qMNCAa93
822Please respect copyright.ＰＥＮＡＮＡWqq5KiUx9e
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。822Please respect copyright.ＰＥＮＡＮＡOEdCzqLp3f
822Please respect copyright.ＰＥＮＡＮＡtFYPGkmX1i
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。822Please respect copyright.ＰＥＮＡＮＡEDbVv3hnhT
822Please respect copyright.ＰＥＮＡＮＡLmj8L7WliZ
822Please respect copyright.ＰＥＮＡＮＡ7eF64KsfEi
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！822Please respect copyright.ＰＥＮＡＮＡAsC32jrLmF
822Please respect copyright.ＰＥＮＡＮＡyTEU6kv4ih
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。822Please respect copyright.ＰＥＮＡＮＡIjJhUEDAMj
822Please respect copyright.ＰＥＮＡＮＡgj3MrR2XwC
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/toc822Please respect copyright.ＰＥＮＡＮＡlgR8xe07Wv
822Please respect copyright.ＰＥＮＡＮＡZvNhlUIK8w
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。822Please respect copyright.ＰＥＮＡＮＡBykncipOoI
822Please respect copyright.ＰＥＮＡＮＡyo3sQhYX3G
Link:822Please respect copyright.ＰＥＮＡＮＡg7a6XDty9c
https://www.penana.com/user/27349/%E8%96%AF%E4%BB%94%E8%81%9E%E8%8C%B1%E8%8E%89/portfolio822Please respect copyright.ＰＥＮＡＮＡTKqReTcoMe
822Please respect copyright.ＰＥＮＡＮＡam0bea74q4
822Please respect copyright.ＰＥＮＡＮＡzLUHdRdgRx
有興趣接收科普資訊的話，歡迎follow IG: potatopigtongue。822Please respect copyright.ＰＥＮＡＮＡztUD6IvboM
822Please respect copyright.ＰＥＮＡＮＡMuAIzuN1zK
822Please respect copyright.ＰＥＮＡＮＡBeRjaHYBuS
Ref2:https://jamanetwork.com/journals/jama/fullarticle/2769612?fbclid=IwAR0sp9eU5V9FOzuLjz6ERw6LRFm-1yx3MJt1OEgqBDQKW1GA5mQeIIi5J7E822Please respect copyright.ＰＥＮＡＮＡZazulTFOHq
Ref3:https://science.sciencemag.org/content/369/6499/77?fbclid=IwAR29zOO06gVsQAC2jLU2uMJi-qcYbniz108Y4kcaWOr1iNuQyVM3jCFMHa4822Please respect copyright.ＰＥＮＡＮＡBwk057gkeV
Ref4:https://www.nature.com/articles/s41586-020-2538-8.pdf822Please respect copyright.ＰＥＮＡＮＡaMXZM14cw3
Ref5:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115629/822Please respect copyright.ＰＥＮＡＮＡlZyqGyaBRR