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Nat Microbiol:研究揭示自然感染病人体内针对H7N9禽流感中和抗体的保护机制

2018-12-02 佚名 微生物研究所

中国科学院微生物研究所团队与英国牛津大学、台湾长庚医院等单位合作于11月26日在国际学术期刊Nature Microbiology(《自然-微生物学》)上发表题为Structure–function analysis of neutralizing antibodies to H7N9 influenza from naturally infected humans 的文章。该研究揭示自然感染病人

中国科学院微生物研究所团队与英国牛津大学、台湾长庚医院等单位合作于11月26日在国际学术期刊Nature Microbiology(《自然-微生物学》)上发表题为Structure–function analysis of neutralizing antibodies to H7N9 influenza from naturally infected humans 的文章。该研究揭示自然感染病人体内针对H7N9禽流感中和抗体的保护机制,对于研制疫苗和防控H7N9禽流感疫情具有重要意义。

2013年中国首次出现了人感染H7N9禽流感病毒的病例,曾一度引发全国各地人们对禽流感特别是H7N9的恐慌。2013年以来,H7N9在我国持续存在、传播并在多个地区引起疫情,特别是2016-2017年的第5波疫情中,因其流行特征和生物学特性较过去发生了较大改变,H7N9高致病性病毒迅速进化,对公共健康和社会经济产生了巨大威胁,尤其需警惕该病毒可能通过基因重配或进一步突变演变成为引起流感大流行的病毒。血凝素(Hemagglutinin,HA)蛋白是流感病毒负责受体识别及膜融合的重要表面糖蛋白,是体内中和抗体的重要靶标和疫苗研制的重要免疫抗原。此前,人们对于人体自然感染H7N9后所产生中和抗体保护机制认识十分有限。

研究团队从2013-2014年中国台湾地区4例(患者L, K, Z, W)输入性H7N9感染病例入手,采集康复病人的血清,发现病人血清能够对H1,H3亚型毒株和2013年H7N9毒株进行有效中和,但是对2016-2017年H7N9毒株的中和活性降低,有些毒株(A/Taiwan/1/2017和A/Guangdong/8H324/2017)甚至不能中和,提示H7N9疫苗研制需进行相应调整和更新。

为进一步探究H7N9感染后机体所产生中和抗体的作用广度和效能,研究团队分离康复病人的外周血单核细胞,用抗原特异性B细胞分选和单细胞克隆技术鉴定出了254株抗体。发现其中73株对H7蛋白有反应性,这73株抗体可以进一步分成两类:一类是能交叉结合H3和H7亚型的抗体有28株,其中只有两株抗体能够中和H7N9病毒,另外一类是H7特异性结合抗体45株,其中15株抗体能够中和H7N9病毒。这些结果表明H7特异性中和抗体在体内起到主要保护作用。同时研究团队对这些中和抗体进行了进一步分析,发现其中3株抗体(L4A-14, L3A-44, L4B-18)能够有效中和多种H7N9毒株,其中效果和广谱性最好的是L4A-14,并在动物模型上证明它能有效预防和治疗2013年和2016-2017年H7N9流行毒株的感染。

研究团队进一步用结构生物学方法解析了3株中和抗体(L4A-14, L3A-44, L4B-18)与H7蛋白复合物的三维结构,揭示3株抗体都作用于HA蛋白头部的受体结合区域,通过阻止病毒与受体结合,从而抑制病毒入侵而起到中和保护作用。其中L3A-44和L4B-18的结合表位比较相似,对HA蛋白受体结合区域L226Q突变和150-loop区域的糖基化都比较敏感;而L4A-14的表位在2016-2017年H7N9毒株中较为保守,只对HA蛋白150-loop区域的糖基化比较敏感。

该研究不仅为开发人感染H7N9禽流感治疗手段提供了方向和理论基础,同时也为H7N9疫苗的研发提供了科学依据。未来研究团队将着手推进临床治疗性抗体开发和疫苗研发等重点工作。

该研究得到Townsend-Jeantet慈善信托基金、台湾长庚医院医学研究项目、人感染H7N9禽流感应急防控研究项目、中科院战略性先导科技专项和国家传染病科技重大专项等的经费支持。

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    2019-04-14 liye789132251
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    2019-07-08 xjy02
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  4. [GetPortalCommentsPageByObjectIdResponse(id=1883453, encodeId=fafd188345324, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sun Apr 14 18:57:00 CST 2019, time=2019-04-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2084462, encodeId=d32f2084462c1, content=<a href='/topic/show?id=61f411e013b' target=_blank style='color:#2F92EE;'>#Micro#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11701, encryptionId=61f411e013b, topicName=Micro)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, 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encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Fri Feb 22 16:57:00 CST 2019, time=2019-02-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1857726, encodeId=9c0b185e72610, content=<a href='/topic/show?id=3f48525849' target=_blank style='color:#2F92EE;'>#CRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5258, encryptionId=3f48525849, topicName=CRO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c30265, createdName=jiafufeng@yaho, createdTime=Wed Nov 13 02:57:00 CST 2019, time=2019-11-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1477563, encodeId=bf1b14e7563e3, content=<a href='/topic/show?id=9f7d8411fc' target=_blank style='color:#2F92EE;'>#H7N9#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8411, encryptionId=9f7d8411fc, topicName=H7N9)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e1f27379114, createdName=ms117281293605716, createdTime=Tue Dec 04 04:57:00 CST 2018, time=2018-12-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1506310, encodeId=06711506310be, content=<a href='/topic/show?id=0e1f84242f' target=_blank style='color:#2F92EE;'>#H7N9禽流感#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8424, encryptionId=0e1f84242f, topicName=H7N9禽流感)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=65ac9737223, createdName=photoman, createdTime=Tue Dec 04 04:57:00 CST 2018, time=2018-12-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1604328, encodeId=ac65160432885, content=<a href='/topic/show?id=71b95335396' target=_blank style='color:#2F92EE;'>#感染病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=53353, encryptionId=71b95335396, topicName=感染病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=337119178396, createdName=xugc, createdTime=Tue Dec 04 04:57:00 CST 2018, time=2018-12-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=354255, encodeId=7166354255dd, content=感谢小编为我们准备了如此丰盛的精神大餐,同时也向作者致谢!认真学习了,点赞!, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Sun Dec 02 15:53:38 CST 2018, time=2018-12-02, status=1, ipAttribution=)]
    2019-02-22 sunylz
  5. [GetPortalCommentsPageByObjectIdResponse(id=1883453, encodeId=fafd188345324, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sun Apr 14 18:57:00 CST 2019, time=2019-04-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2084462, encodeId=d32f2084462c1, content=<a href='/topic/show?id=61f411e013b' target=_blank style='color:#2F92EE;'>#Micro#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11701, encryptionId=61f411e013b, topicName=Micro)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, 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encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Fri Feb 22 16:57:00 CST 2019, time=2019-02-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1857726, encodeId=9c0b185e72610, content=<a href='/topic/show?id=3f48525849' target=_blank style='color:#2F92EE;'>#CRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5258, encryptionId=3f48525849, topicName=CRO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c30265, createdName=jiafufeng@yaho, createdTime=Wed Nov 13 02:57:00 CST 2019, time=2019-11-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1477563, encodeId=bf1b14e7563e3, content=<a href='/topic/show?id=9f7d8411fc' target=_blank style='color:#2F92EE;'>#H7N9#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8411, encryptionId=9f7d8411fc, topicName=H7N9)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e1f27379114, createdName=ms117281293605716, createdTime=Tue Dec 04 04:57:00 CST 2018, time=2018-12-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1506310, encodeId=06711506310be, content=<a href='/topic/show?id=0e1f84242f' target=_blank style='color:#2F92EE;'>#H7N9禽流感#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8424, encryptionId=0e1f84242f, topicName=H7N9禽流感)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=65ac9737223, createdName=photoman, createdTime=Tue Dec 04 04:57:00 CST 2018, time=2018-12-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1604328, encodeId=ac65160432885, content=<a href='/topic/show?id=71b95335396' target=_blank style='color:#2F92EE;'>#感染病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=53353, encryptionId=71b95335396, topicName=感染病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=337119178396, createdName=xugc, createdTime=Tue Dec 04 04:57:00 CST 2018, time=2018-12-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=354255, encodeId=7166354255dd, content=感谢小编为我们准备了如此丰盛的精神大餐,同时也向作者致谢!认真学习了,点赞!, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Sun Dec 02 15:53:38 CST 2018, time=2018-12-02, status=1, ipAttribution=)]
  6. [GetPortalCommentsPageByObjectIdResponse(id=1883453, encodeId=fafd188345324, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=59, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Sun Apr 14 18:57:00 CST 2019, time=2019-04-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2084462, encodeId=d32f2084462c1, content=<a href='/topic/show?id=61f411e013b' target=_blank style='color:#2F92EE;'>#Micro#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=65, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11701, encryptionId=61f411e013b, topicName=Micro)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d59291, 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encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Fri Feb 22 16:57:00 CST 2019, time=2019-02-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1857726, encodeId=9c0b185e72610, content=<a href='/topic/show?id=3f48525849' target=_blank style='color:#2F92EE;'>#CRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5258, encryptionId=3f48525849, topicName=CRO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c30265, createdName=jiafufeng@yaho, createdTime=Wed Nov 13 02:57:00 CST 2019, time=2019-11-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1477563, encodeId=bf1b14e7563e3, content=<a href='/topic/show?id=9f7d8411fc' target=_blank style='color:#2F92EE;'>#H7N9#</a>, beContent=null, objectType=article, channel=null, 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  7. 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encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Fri Feb 22 16:57:00 CST 2019, time=2019-02-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1857726, encodeId=9c0b185e72610, content=<a href='/topic/show?id=3f48525849' target=_blank style='color:#2F92EE;'>#CRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5258, encryptionId=3f48525849, topicName=CRO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c30265, createdName=jiafufeng@yaho, createdTime=Wed Nov 13 02:57:00 CST 2019, time=2019-11-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1477563, encodeId=bf1b14e7563e3, content=<a href='/topic/show?id=9f7d8411fc' target=_blank style='color:#2F92EE;'>#H7N9#</a>, beContent=null, objectType=article, channel=null, 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  8. 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level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8411, encryptionId=9f7d8411fc, topicName=H7N9)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e1f27379114, createdName=ms117281293605716, createdTime=Tue Dec 04 04:57:00 CST 2018, time=2018-12-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1506310, encodeId=06711506310be, content=<a href='/topic/show?id=0e1f84242f' target=_blank style='color:#2F92EE;'>#H7N9禽流感#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8424, encryptionId=0e1f84242f, topicName=H7N9禽流感)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=65ac9737223, createdName=photoman, createdTime=Tue Dec 04 04:57:00 CST 2018, time=2018-12-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1604328, encodeId=ac65160432885, content=<a 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CST 2018, time=2018-12-02, status=1, ipAttribution=)]
    2018-12-04 xugc
  9. 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encryptionId=4f26341994, topicName=Bio)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=12de429, createdName=sunylz, createdTime=Fri Feb 22 16:57:00 CST 2019, time=2019-02-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1857726, encodeId=9c0b185e72610, content=<a href='/topic/show?id=3f48525849' target=_blank style='color:#2F92EE;'>#CRO#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=66, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5258, encryptionId=3f48525849, topicName=CRO)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c30265, createdName=jiafufeng@yaho, createdTime=Wed Nov 13 02:57:00 CST 2019, time=2019-11-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1477563, encodeId=bf1b14e7563e3, content=<a href='/topic/show?id=9f7d8411fc' target=_blank style='color:#2F92EE;'>#H7N9#</a>, beContent=null, objectType=article, channel=null, 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href='/topic/show?id=71b95335396' target=_blank style='color:#2F92EE;'>#感染病#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=84, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=53353, encryptionId=71b95335396, topicName=感染病)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=337119178396, createdName=xugc, createdTime=Tue Dec 04 04:57:00 CST 2018, time=2018-12-04, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=354255, encodeId=7166354255dd, content=感谢小编为我们准备了如此丰盛的精神大餐,同时也向作者致谢!认真学习了,点赞!, beContent=null, objectType=article, channel=null, level=null, likeNumber=94, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Sun Dec 02 15:53:38 CST 2018, time=2018-12-02, status=1, ipAttribution=)]
    2018-12-02 1dd8a7c5m95(暂无匿称)

    感谢小编为我们准备了如此丰盛的精神大餐,同时也向作者致谢!认真学习了,点赞!

    0

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