抗體依賴增強作用

抗體依賴增強作用（英語：Antibody-dependent enhancement，縮寫：ADE）又稱抗體依賴增強感染效應、抗體依賴性增強，是指一些次優的抗體（一般為可結合病毒的非中和抗體）與病毒結合後，不僅不能防止病毒侵入人體細胞，反而會增強病毒感染免疫細胞、促進病毒在體內的複製，惡化疾病的嚴重度或誘發更嚴重的額外徵候。^[1]^[2]

機制

抗體依賴性增強的機制有兩種：

次優抗體與病毒結合後，其Fc段（英語：Fragment crystallizable region）再與免疫細胞表面表達的Fc受體結合，接着使病毒進入免疫細胞，但病毒因抗體對抗原的結合力不佳而未被中和分解，反而在免疫細胞中複製增殖；此機制已在人類的登革熱感染與貓的貓冠狀病毒感染中觀察到^[3]。例如：感染過登革熱的患者若再被另一亞型的登革熱病毒感染，會依之前的免疫記憶產生中和力較低的抗體，而可能發生抗體依賴增強感染的效應，這也是上述兩種疾病疫苗開發困難的原因之一^[4]。簡言之，病毒「欺騙」了免疫細胞的吞噬過程，將宿主的抗體變成了特洛伊木馬。
次優抗體和抗原結合後，與補體相互作用，接着促進發炎反應；例如人類呼吸道合胞病毒（RSV）與麻疹病毒感染時即可能在呼吸道組織發生抗體依賴性增強，活化數種細胞激素與補體而造成發炎，嚴重者甚至可能導致急性呼吸窘迫綜合症^[3]。

引發之病毒種類

除上述病毒（登革熱病毒、貓冠狀病毒、人類呼吸道合胞病毒、麻疹病毒）外，有體外實驗顯示人類免疫缺乏病毒、伊波拉病毒、流感病毒、黃熱病毒與SARS冠狀病毒^[5]^[6]^[7]感染皆可能發生抗體依賴性增強^[3]。

2020年，有反疫苗活動家以此機制為拒絕施打疫苗的理由，但目前未知人體施打疫苗後是否會出現此現象^[8]^[9]。

參見

抗原原罪
阻斷抗體（英語：Blocking antibody）：指與抗原結合後無中和能力，卻阻礙其他抗體或免疫細胞結合該病原的抗體
鈎狀效應（英語：hook effect）：指免疫分析等體外實驗中，當抗原或抗體含量過高時，訊號（免疫複合物（英語：Immune complex））反而降低的現象

參考文獻

^ Tirado SM, Yoon KJ. Antibody-dependent enhancement of virus infection and disease. Viral Immunology. 2003, 16 (1): 69–86. PMID 12725690. doi:10.1089/088282403763635465.
^ Kulkarni, Ruta. Antibody-Dependent Enhancement of Viral Infections. Dynamics of Immune Activation in Viral Diseases. 2019-11-05: 9–41 [2020-09-23]. PMC 7119964 . doi:10.1007/978-981-15-1045-8_2. （原始內容存檔於2020-12-07）.
^ ^3.0 ^3.1 ^3.2 Lee WS, Wheatley AK, Kent SJ, DeKosky BJ. Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies.. Nat Microbiol. 2020, 5 (10): 1185–1191. PMID 32908214. doi:10.1038/s41564-020-00789-5.
^ Shukla R, Ramasamy V, Shanmugam RK, Ahuja R, Khanna N. Antibody-Dependent Enhancement: A Challenge for Developing a Safe Dengue Vaccine.. Front Cell Infect Microbiol. 2020, 10: 572681. PMC 7642463 . PMID 33194810. doi:10.3389/fcimb.2020.572681.
^ Wan Y, Shang J, Sun S, Tai W, Chen J, Geng Q; et al. Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry.. J Virol. 2020, 94 (5). PMC 7022351 . PMID 31826992. doi:10.1128/JVI.02015-19.
^ Jaume M, Yip MS, Cheung CY, Leung HL, Li PH, Kien F; et al. Anti-severe acute respiratory syndrome coronavirus spike antibodies trigger infection of human immune cells via a pH- and cysteine protease-independent FcγR pathway.. J Virol. 2011, 85 (20): 10582–97. PMC 3187504 . PMID 21775467. doi:10.1128/JVI.00671-11.
^ Eroshenko, Nikolai; Gill, Taylor; Keaveney, Marianna K.; Church, George M.; Trevejo, Jose M.; Rajaniemi, Hannu. Implications of antibody-dependent enhancement of infection for SARS-CoV-2 countermeasures. Nature Biotechnology. 2020-07, 38 (7): 789–791 [2022-01-10]. ISSN 1546-1696. doi:10.1038/s41587-020-0577-1. （原始內容存檔於2021-06-04）（英語）.
^ Teoh F (編). No evidence that COVID-19 vaccines cause more severe disease; antibody-dependent enhancement has not been observed in clinical trials (Fact check). Health Feedback. 2020-11-27 [2021-04-29]. （原始內容存檔於2021-02-04）.
^ Gorski DH. It was inevitable that antivaxxers would claim that COVID-19 vaccines make females infertile. Science-Based Medicine. 2020-12-14 [2021-04-29]. （原始內容存檔於2021-02-09）. the overall petition ... spends far more verbiage on PCR, Sanger sequencing, and the not-unreasonable but thus far not observed concern about antibody-dependent enhancement (ADE) due to a vaccine

[Tirado_2003-1] Tirado SM, Yoon KJ. Antibody-dependent enhancement of virus infection and disease. Viral Immunology. 2003, 16 (1): 69–86. PMID 12725690. doi:10.1089/088282403763635465.

[2] Kulkarni, Ruta. Antibody-Dependent Enhancement of Viral Infections. Dynamics of Immune Activation in Viral Diseases. 2019-11-05: 9–41 [2020-09-23]. PMC 7119964 . doi:10.1007/978-981-15-1045-8_2. （原始內容存檔於2020-12-07）.

[pmid32908214-3] 3.0 ^3.1 ^3.2 Lee WS, Wheatley AK, Kent SJ, DeKosky BJ. Antibody-dependent enhancement and SARS-CoV-2 vaccines and therapies.. Nat Microbiol. 2020, 5 (10): 1185–1191. PMID 32908214. doi:10.1038/s41564-020-00789-5.

[pmid33194810-4] Shukla R, Ramasamy V, Shanmugam RK, Ahuja R, Khanna N. Antibody-Dependent Enhancement: A Challenge for Developing a Safe Dengue Vaccine.. Front Cell Infect Microbiol. 2020, 10: 572681. PMC 7642463 . PMID 33194810. doi:10.3389/fcimb.2020.572681.

[pmid31826992-5] Wan Y, Shang J, Sun S, Tai W, Chen J, Geng Q; et al. Molecular Mechanism for Antibody-Dependent Enhancement of Coronavirus Entry.. J Virol. 2020, 94 (5). PMC 7022351 . PMID 31826992. doi:10.1128/JVI.02015-19.

[pmid21775467-6] Jaume M, Yip MS, Cheung CY, Leung HL, Li PH, Kien F; et al. Anti-severe acute respiratory syndrome coronavirus spike antibodies trigger infection of human immune cells via a pH- and cysteine protease-independent FcγR pathway.. J Virol. 2011, 85 (20): 10582–97. PMC 3187504 . PMID 21775467. doi:10.1128/JVI.00671-11.

[7] Eroshenko, Nikolai; Gill, Taylor; Keaveney, Marianna K.; Church, George M.; Trevejo, Jose M.; Rajaniemi, Hannu. Implications of antibody-dependent enhancement of infection for SARS-CoV-2 countermeasures. Nature Biotechnology. 2020-07, 38 (7): 789–791 [2022-01-10]. ISSN 1546-1696. doi:10.1038/s41587-020-0577-1. （原始內容存檔於2021-06-04）（英語）.

[8] Teoh F (編). No evidence that COVID-19 vaccines cause more severe disease; antibody-dependent enhancement has not been observed in clinical trials (Fact check). Health Feedback. 2020-11-27 [2021-04-29]. （原始內容存檔於2021-02-04）.

[sbm-9] Gorski DH. It was inevitable that antivaxxers would claim that COVID-19 vaccines make females infertile. Science-Based Medicine. 2020-12-14 [2021-04-29]. （原始內容存檔於2021-02-09）. the overall petition ... spends far more verbiage on PCR, Sanger sequencing, and the not-unreasonable but thus far not observed concern about antibody-dependent enhancement (ADE) due to a vaccine

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