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標題: Evaluation of the vaccine potential of the Staphylococcus aureus specific monoclonal antibody 1D11B and its target antigen
金黃葡萄球菌專一單株抗體 1D11B 及其目標抗原之疫苗潛力評估
作者: 林偉名
Wei-Ming Lin
關鍵字: 金黃葡萄球菌
Staphylococcus aureus
therapeutic antibody
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摘要: Staphylococcus aureus (SA) causes a variety of diseases ranging from skin infection to life-threatening diseases. Most isolated clinical SA strains show antibiotic resistance; thus developing effective protection strategies against SA infection are urgently needed. Monoclonal antibody (mAb) 1D11B that was raised against heat killed SA presumably recognizes a surface-exposed epitope. This study investigated the therapeutic potential of the mAb 1D11B and identified its target antigen. To achieve the first goal, 0.4 mg / 200 μl purified mAb were intraperitoneally injected into each mouse 16 h before challenge with SA Tc1040, a clinical isolate, by intraperitoneal injection or intratracheal instillation. No protection was observed in mice challenged by intraperitoneal injection assessed by either the survival rate or blood bacterial counts. However, SA recovered from the lungs of mAb 1D11B administered mice were significantly less than mice received a nonspecific mAb 2F3B. These results indicate that mAb 1D11B may protect the mice against the Staphylococcus aureus induced pneumonia and its target antigen may be a good vaccine candidate. The target antigen of 1D11B was previously identified by mass spectrometry to be the lipoprotein MntC (manganese transporter protein C). In this study, the lipidated Ag473-MntC fusion protein (L-Ag473-MntC) and the lipidated MntC (L-MntC) were produced and used to immunize BALB/c mice in the absence of adjuvants. Anti-MntC antibodies were detected in all immunized mice and anti-Ag473 antibodies were also detected in the (L-Ag473-MntC) immunized mice. In contrast to the protection assays conducted in CD-1 mice by the other group, immunization with L-MntC or L-Ag473-MntC did not confer protection against SA infection. Whether the different results are resulted from the mouse strain or immunogen preparation remains to be determind.
Staphylococcus aureus (SA) 為人類伺機性病原菌,可廣泛造成人類多種疾病的發生,包含致命性的疾病如肺炎、骨髓炎、心內膜炎及敗血症等,由於抗生素的過度使用導致 SA 多重抗藥性菌株的出現,因此迫切需要發展 SA 的疫苗。本實驗室以 SA 全菌免疫小鼠進行融合瘤細胞製備,經篩選獲得 SA 專一單株抗體 1D11B,推測其 epitope 應該位於菌體表面,本論文評估單株抗體 1D11B 是否具有治療性抗體潛力及確認其抗原蛋白質身分。抗體保護力評估以 0.4 mg / 200 μl 純化後單株抗體腹腔注射小鼠,16 小時後以腹腔注射或氣管滴灌感染 SA 臨床菌株 Tc1040 進行攻毒試驗。腹腔注射攻毒在存活率觀察及血液菌落數分析皆顯示無保護力,然而氣管滴灌攻毒顯示注射單株抗體 1D11B 的小鼠肺臟菌落數比注射非專一單株抗體 2F3B 有顯著減少。以上結果指出單株抗體 1D11B 可保護小鼠抵抗 SA 引發的肺炎,而 1D11B 的目標抗原可能為良好的疫苗候選抗原。本實驗室由質譜儀分析確認單株抗體 1D11B 之目標抗原為脂蛋白質 MntC (manganese transport protein C),本論文純化 lipidated Ag473-MntC (L-Ag473-MntC) 融合蛋白質與 L-MntC 重組蛋白質,不加佐劑免疫 BALB/c 小鼠。免疫後所有小鼠皆偵測到 anti-MntC 抗體產生,且免疫 L-Ag473-MntC 的小鼠也偵測到含有 anti-Ag473 抗體,但是在 SA 的攻毒試驗中顯示無保護力。有研究團隊指出免疫 MntC 在 CD-1 小鼠可產生保護性免疫反應,本論文之實驗結果是否由於不同的小鼠品系或免疫原製備方法所造成,仍需進行實驗確認。
文章公開時間: 2017-08-31
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