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。801Please respect copyright.PENANAWLk95RxbRE
801Please respect copyright.PENANAUvUQIe03k3
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。801Please respect copyright.PENANAmAi4rkdGYu801Please respect copyright.PENANAOZRcFSgIzY
801Please respect copyright.PENANAWN5AgxJOdt
(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。801Please respect copyright.PENANAqr3kZkAUjA
801Please respect copyright.PENANAV8SfimzkwI
下列為Sinovac製作滅活病毒疫苗的扼要流程(Ref3)801Please respect copyright.PENANADDlLxgoVnq
801Please respect copyright.PENANA89WU49mssn
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。801Please respect copyright.PENANAgjfTkH9OL8
801Please respect copyright.PENANA4L1Aiz43ap
2.經過數輪實驗室細胞的培植,使病毒數量增加。801Please respect copyright.PENANAS4lVEpx6Tl
801Please respect copyright.PENANA0M6WTuPunm
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。801Please respect copyright.PENANAn9aXZedxjT
801Please respect copyright.PENANAYMdgLdE7hI
4.將其製成可注射的疫苗。801Please respect copyright.PENANANRU8QDTWn6
801Please respect copyright.PENANAG21dppGFtU801Please respect copyright.PENANAxkCZal9W8T
801Please respect copyright.PENANAFX3BC4jnmV
(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。801Please respect copyright.PENANA90rfAlFiTG
801Please respect copyright.PENANAVepBu0psZz
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。801Please respect copyright.PENANAMNnVKKmotM
https://www.penana.com/article/466568801Please respect copyright.PENANAxA9oMzd4uj
801Please respect copyright.PENANA7sy45aHIxe801Please respect copyright.PENANA8aLTIvJ6VF
801Please respect copyright.PENANAWeYVCyAMNX
801Please respect copyright.PENANAgaw7GBK8V5
801Please respect copyright.PENANAVirnFWiii2
801Please respect copyright.PENANALa8uOOokmA801Please respect copyright.PENANAaiyw503D7M
801Please respect copyright.PENANA0FD3EuG8MP
(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。801Please respect copyright.PENANAxzAMNwTCJu
801Please respect copyright.PENANAIeuMw7TqOZ
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。801Please respect copyright.PENANAPs8xAjo9Lv
801Please respect copyright.PENANAwIMqi4M76J
1.抗體與病毒的S protein合併,801Please respect copyright.PENANA1Zds1XqxEL
防止條件1的達成。801Please respect copyright.PENANAdQpyl4RJ8R
801Please respect copyright.PENANAv3ZXWpE40T
2.抗體與病毒其他位置合併,801Please respect copyright.PENANA8KROFRva6X
防止條件3的達成。801Please respect copyright.PENANA9N0bJxXs1m
801Please respect copyright.PENANAPs7CmmKlWz801Please respect copyright.PENANALBk0ZIpBju
801Please respect copyright.PENANAOuOg9fHQ1P
(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。801Please respect copyright.PENANAc0DwDYXlA7
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。801Please respect copyright.PENANAN0EtUtwWuv
801Please respect copyright.PENANA19fFxKLBOv
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。801Please respect copyright.PENANAc9gCSPXlIZ
801Please respect copyright.PENANA6gNtiEUddE
801Please respect copyright.PENANAznZS49loYj801Please respect copyright.PENANAAOIbo4ZCxX
801Please respect copyright.PENANAblCRcF8V6I
(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;801Please respect copyright.PENANAsnBi8d5TGa
簡單來說,就是抗體適得其反地協助病毒入侵人體細胞。801Please respect copyright.PENANAAML50VWND5
801Please respect copyright.PENANA5hSbJJTewq
免疫細胞的表面上,有著接收器識辨抗體的某個區域。801Please respect copyright.PENANAAVdM8Zy84e
801Please respect copyright.PENANAWaDeQPcmHM
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。801Please respect copyright.PENANA0GWADvkhQk
801Please respect copyright.PENANAYrLBEybgUP
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。801Please respect copyright.PENANAMZiGhxADmx
801Please respect copyright.PENANAPQJ5kvef0i801Please respect copyright.PENANAmLeWyEIEqq
801Please respect copyright.PENANA32UBMe96kz
(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。801Please respect copyright.PENANAqltEVPyAsr
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。801Please respect copyright.PENANAmgWCiBYefS
801Please respect copyright.PENANAdH0VqIJlkJ
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。801Please respect copyright.PENANABcziPw5uEQ
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。801Please respect copyright.PENANAJGbKwhk0gF
801Please respect copyright.PENANAzRhH6Ur35N801Please respect copyright.PENANAcSuvDnmaZ3
801Please respect copyright.PENANAtY3G1Qin3w
(圖8)ADE這現象,科學家一直以來均有記錄及研究。(Ref4)801Please respect copyright.PENANAw98KYypLPT
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。801Please respect copyright.PENANArhyIXEpawo
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。801Please respect copyright.PENANAZwgvIgjAx2
801Please respect copyright.PENANA5B6QG94H0W
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。801Please respect copyright.PENANAI2c7JksujX
801Please respect copyright.PENANARBGThqHW1V801Please respect copyright.PENANAJafkks1Ujh
801Please respect copyright.PENANAKCARNspQOl
(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)801Please respect copyright.PENANAIHhC2Tw3hy
801Please respect copyright.PENANANdhoNoiY0T
武肺會否出現同樣現象,暫時尚未清楚。801Please respect copyright.PENANAwuBz4QCGVJ
801Please respect copyright.PENANAjwUJB2bSjT
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。801Please respect copyright.PENANAPVkiNts4Pa
801Please respect copyright.PENANALJ4bOgEWAM
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。801Please respect copyright.PENANA9gdm1v2NOw
801Please respect copyright.PENANAkIQMbWcFoT
801Please respect copyright.PENANA1CvmrMBsGF
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!801Please respect copyright.PENANArxoWOKRALK
801Please respect copyright.PENANAWan08XWn9Q
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。801Please respect copyright.PENANAxbCMuvh9YF
801Please respect copyright.PENANAPqpCzCpbKv
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/toc801Please respect copyright.PENANAWA7ha4RAff
801Please respect copyright.PENANAatmJ124qPi
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。801Please respect copyright.PENANAAmOCHV0JWX
801Please respect copyright.PENANAKLeFZWpoCq
Link:801Please respect copyright.PENANAMPullaFl57
https://www.penana.com/user/27349/%E8%96%AF%E4%BB%94%E8%81%9E%E8%8C%B1%E8%8E%89/portfolio801Please respect copyright.PENANAkYO8FF8Y1c
801Please respect copyright.PENANAArDvjZqMv5
801Please respect copyright.PENANAN4prNwd8GH
有興趣接收科普資訊的話,歡迎follow IG: potatopigtongue。801Please respect copyright.PENANAtrMiRcUWN0
801Please respect copyright.PENANAK11xAw9kfS
801Please respect copyright.PENANAuE6P4mgQS4
Ref2:https://jamanetwork.com/journals/jama/fullarticle/2769612?fbclid=IwAR0sp9eU5V9FOzuLjz6ERw6LRFm-1yx3MJt1OEgqBDQKW1GA5mQeIIi5J7E801Please respect copyright.PENANASSIeGT69nX
Ref3:https://science.sciencemag.org/content/369/6499/77?fbclid=IwAR29zOO06gVsQAC2jLU2uMJi-qcYbniz108Y4kcaWOr1iNuQyVM3jCFMHa4801Please respect copyright.PENANAw69RrH3Nm4
Ref4:https://www.nature.com/articles/s41586-020-2538-8.pdf801Please respect copyright.PENANACrvRZDfZjQ
Ref5:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7115629/801Please respect copyright.PENANAgzEQnhhNLx