CN113813378A - 蛋黄igy多克隆抗体中和,抑制新冠病毒covid-19的作用 - Google Patents
蛋黄igy多克隆抗体中和,抑制新冠病毒covid-19的作用 Download PDFInfo
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Abstract
新冠状病毒COVID‑19,N蛋白免疫鸡在鸡蛋黄有IGY多克隆抗体,试验证明这种IGY有中和,抑制新冠状病毒COVID‑19作用,这种来自天然食品作为预防和治疗新冠状病毒,人们容易接受,而且价格便宜操作简单,是一种理想的预防和治疗新冠状病毒COVID‑19的药物或保健食品。
Description
技术领域:医学免疫治疗领域。
背景技术:使用抗原免疫鸡可产生抗体转移和积累于蛋黄中,从蛋黄提取的抗体主要成分是IGY。
IGY理化性质:
1,在65℃一个小时活性不变,可以进行巴氏消毒消灭病原体又可以维持活性
2,在酸性环境PH3-11环境中仍有有比较高的活性。
3,IGY在体外模拟试验对胃蛋白酶,胰蛋白酶处理后仍有活性。
上述内容IgY抗体可作为药用或保健品口服
IgY功能:
重多文献报导IGY对疾病防治和诊断功能的报导。值得提出的著者杜洪桥综述文章,【卵黄抗体IGY在临床医学中的应用】附件一,抗病毒治疗,胡国柱等以灭活SAS-CoV免疫产蛋母鸡用水稀释法获得IGY,研究发现该抗体提取液稀释1∶512时扔可以中和SARS-CoY保护50%的VEROE6的细胞不被SARS-CoV感染。它与SARS患者恢复期血清中和SARS-CoV的效价相同。这说明抗SARS-CoV IGY多克隆抗体可阻断S蛋白与细胞受体结合,抑制SARS-CoV感染VEAOE6细胞。
实验员苗成等:利用大肠癌细胞免疫产蛋母鸡获得IGY,取10只裸鼠在背部注射(种植)大肠癌细胞,分两组,试验组5只鼠口服IGY抗体,另5只为对照组,结果试验组5只裸鼠3只没有肿瘤生长,2只肿瘤生长R1-2mm.对照组在肿瘤细胞注射部位全部生长肿瘤R3-5mm.附件二,说明IGY有抑制肿瘤细胞生长作用。
发明内容:
一、制备N蛋白
1 2019-nCoV
从NCBI上查找到2019-nCov基因序列,GenBank号为NC_045512,序列为1260bp,如下所示,送去南京金斯瑞公司合成,经过密码子优化,通过限制性内切酶EcoRI和XhoI构建至pET-28a表达载体上,记为N蛋白。
2019-nCoV原始序列(1260bp):
N蛋白氨基酸序列:
2转化大肠杆菌感受态细胞BL21
合成后是质粒干粉4ug。加入40uL TE Buffer溶解为100ng/uL。转化至大肠杆菌感受态细胞BL21,涂平板培养过夜。挑取单菌落摇菌,菌液鉴定正确后即可进行蛋白表达。
3 N蛋白的表达和纯化
3.1 N蛋白的表达
取鉴定正确的菌液在小瓶中进行活化,过夜培养,第二天转入大瓶摇菌,生长处于对数期,OD600为0.6~0.8时,加入终浓度为0.01mM的IPTG诱导表达目的蛋白,诱导过夜培养,离心9000rpm,10min,收集菌体,-20度冰箱保存备用。
3.2 N蛋白的纯化
称取菌体,按1∶10加入破菌液进行超声破碎,同时实验,确定N蛋白表达在上清。超声破碎后离心收集上清,过镍柱纯化,梯度浓度咪唑缓冲液洗脱目的蛋白,根据SDS-PAGE凝胶电泳胶图,选取洗脱纯度和浓度都较高的洗脱样品,透析出去咪唑,测浓度后保存备用。
N蛋白氨基酸序列:
2转化大肠杆菌感受态细胞BL21
合成后是质粒干粉4ug。加入40uL TE Buffer溶解为100ng/uL。转化至大肠杆菌感受态细胞BL21,涂平板培养过夜。挑取单菌落摇菌,菌液鉴定正确后即可进行蛋白表达。
3 N蛋白的表达和纯化
3.1 N蛋白的表达
取鉴定正确的菌液在小瓶中进行活化,过夜培养,第二天转入大瓶摇菌,生长处于对数期,OD600为0.6~0.8时,加入终浓度为0.01mM的IPTG诱导表达目的蛋白,诱导过夜培养,离心9000rpm,10min,收集菌体,-20度冰箱保存备用。
3.2 N蛋白的纯化
称取菌体,按1∶10加入破菌液进行超声破碎,同时实验,确定N蛋白表达在上清。超声破碎后离心收集上清,过镍柱纯化,梯度浓度咪唑缓冲液洗脱目的蛋白,根据SDS-PAGE凝胶电泳胶图,选取洗脱纯度和浓度都较高的洗脱样品,透析出去咪唑,测浓度后保存备用。
二、N蛋白免疫及纯化
取N蛋白免疫产蛋母鸡。
每只母鸡N蛋白2mg加完全佐剂加大肠杆菌不耐热蛋白混合,注射鸡的翅膀皮下,10-15天进行第二次加不完全佐剂免疫,50-60天取蛋纯化。纯化方法使用水纯化法,获得IGY抗体每个蛋产率100mg左右
三、亲和力鉴定
1,ELISA方法:检测N蛋白免疫IGY活性8ng/ml,1,6ng/ml。附件三。ELSA检测报告。
2,新冠状病毒COVID-19抗体检测胶体金方法,原理是人体感染新冠状病毒COVID-19血液中出现IgM,IgG抗体,使用N蛋白标记金,硝酸纤维膜包被IgM,IgG抗抗体。人体被新冠状病毒covid-19感染的IgM,IgG与N蛋白有亲和力与N蛋白结合也标上金颗粒,层析作用达到硝酸纤维膜上与IgM,IgG抗抗体结合出现红线为阳性。证明N蛋白与新冠状病毒covid-19有同源性亲和力。。附件四,
四,综合上述N蛋白免疫禽类获得卵黄IGY多克隆抗体,服用有预防,治疗新冠状病毒COVID-19的作用。
Claims (4)
1.新冠状病毒COVID-19,N蛋白免疫产蛋母鸡,获得卵黄IGY多克隆抗体有中和,抑制新冠状病毒COVID-19作用,能够预防治疗新冠状病毒COVID-19。
2.根据权利1,N蛋白作为免疫原,灭活新冠状病毒COVID-19,和从新冠状病毒COVID-19提取或重组同源性所有的蛋白质如S蛋白都属于免疫原。
3.根据权利1,鸡属于禽类,凡是禽类都可以免疫产生卵黄IGY。
4.免疫佐剂大肠杆菌不耐热蛋白有强化免疫的作用。
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