Science:为获取疫苗探路,17名志愿者让血吸虫钻入体内

2018-02-24 贺梨萍 澎湃新闻

在非洲、中东和拉丁美洲,数百万人患有血吸虫病,每年的致死人数则达上***。目前,能与该疾病对抗的只有一种很老且效果不佳的药物——吡喹酮。荷兰的一个实验室从2017年开始,试图通过血吸虫人体感染实验来获得疫苗。



据《科学》(Science)官网报道,荷兰莱顿大学医疗中心传染病医生Meta Roestenberg在日前对4名志愿者完成了感染实验。截至目前,已有17位志愿者愿意让该实验室培养出的曼氏血吸虫(Schistosoma mansoni)进入自己体内,此前的13位志愿者无一发生强烈的过敏反应或高烧现象。

曼氏血吸虫是引起血吸虫病的五大水生蠕虫物种之一,它们通常寄生于红螺等螺体中。

非洲湖泊中这样的螺群单单一天就能散播出数百万这样的幼虫到水里。这些幼虫会经皮肤进入人体,随后转移至肺部,并在肺部成熟和交配。雌雄寄生虫待在一起,进入肠道血管中,最终它们可以在这里寄存数年,每天产卵数以百计。

大多数卵随尿液和粪便排出,如果这些排泄物重新流入湖泊中,或许会感染新的螺群。但还有一些卵会滞留在肝脏、肾脏,或脾脏中,从而导致器官损害,引起疼痛、失血、营养不良,有时甚至导致死亡。

20个寄生虫进入每位志愿者

报道中提到,Roestenberg实验室在数十年以前就重建了寄生虫的生命周期,当然不是在人体里而是在另一种脊椎动物仓鼠身上。研究人员可以在仓鼠身上繁殖和研究曼氏血吸虫。

当天的12时5分,一名实验室技术人员将一个6孔、每孔有一只红螺的培养板置入电热恒温水槽,并用强光照射。随后,从红螺中涌出上百个小小的幼体寄生虫。从这一刻起,Roestenberg当天的这项工作开始计时。

在接下来的4个小时内,Roestenberg要展开一项独特但具有争议的实验:让这些寄生虫钻进4名健康志愿者的手臂。如果等待的时间太长,这些寄生虫会死掉。

1个小时之后,也就是下午1时5分,技术人员将培养板从恒温水槽中取出,准备收集寄生幼虫。透过显微镜,可以看到这些幼虫疯狂蠕动。另一名技术人员从培养板中取出一滴,稀释并加入碘酒杀死这些幼虫,随后对不再蠕动的死亡幼虫进行计数。通过这一步,研究人员可以计算出培养板的孔里一共有574个幼虫。当天实验只需用到80个寄生幼虫,每位志愿者20个。

下午1时35分,Roestenberg走进志愿者将被感染的房间。她打开一个透明的塑料容器,里面有肾上腺素、抗组胺药和糖皮质激素。“这是一个应急箱。”Roestenberg表示,以防在志愿者身上出现强烈的过敏反应。

在现实情况中,雄性和雌性寄生虫都会使人体感染,但Roestenberg实验中只用到了雄性。以此避免产卵,Roestenberg认为这样就不会出现临床症状。这项研究会在12周后结束,志愿者会随后将接受吡喹酮治疗。

下午2时35分,感染实验正式开始。志愿者伸出他们的手臂,一个直径几厘米的小的金属注射器会贴在他们的皮肤上。助手吸取几滴精确计数有20个寄生虫的悬液到注射器中。志愿者们很紧张,但他们说他们是受到激励的。其中一名年轻的科学家提到,“我喜欢这项研究因为它和疫苗有关,我曾经也在这一领域内工作。”他身边的一名女性则说,她来自东非,知道这种疾病。这些志愿者每人也会获得1000欧元。

一旦接受感染实验之后,志愿者将每周回到实验室一趟。研究人员会通过一种叫做“CAA”的分子测试他们的血液,CAA正是来源于寄生虫。CAA的存在表明这些寄生虫在人体内仍然存活,而在未来的实验中,如果没有CAA则表明一种疫苗或者药物有效。

感染5分钟后,一名志愿者提到“有一点儿痒痒的”。半个小时之后,感染注射的悬液会移到前臂,寄生虫进入它们新的宿主,志愿者的手臂上留下一个红点。当天下午4点,这项实验正式结束。

不排除在人体内存活5到10年

鉴于目前血吸虫病没有很好的治疗途径,Roestenberg认为人体传染实验或许可以加速该疾病新干预措施的开发。Roestenberg设计的实验可以避免寄生虫在体内繁殖,“志愿者的风险是极低的”。

但在外界看来,这项实验对志愿者来说风险并不是足够低。一些科学家就此争论,他们认为实验并不能保证在结束的时候志愿者身上的寄生虫能完全清除。“我自己不会去做这项研究的志愿者,如果我有儿子或者女儿,他们想要去做志愿者的话我也会建议不要去。”美国佐治亚大学血吸虫病研究者Daniel Colley表示。

Colley还强调,吡喹酮“不是特别有效”。但Roestenberg却说,即使实验失败了,志愿者也不必担心。“伦理委员会问我:‘如果治疗之后还有一个寄生虫在人体内存活,这会对人体造成什么影响?’我回答:‘他们很可能会活到100岁。’”

风险确实很低,Colley赞同这一点。但是,曼氏血吸虫的平均寿命是5到10年。“这是一段很长的时间,血吸虫会生存在你的血管中。”

值得注意的是,目前人体感染疟疾、霍乱和流感的研究越来越多,但血吸虫方面人体研究此前尚未展开,一部分原因就在于曼氏血吸虫带来的损伤是不可逆的。目前这项研究始于2017年,它的目标是验证Roestenberg的感染模型是否安全。如果安全,她希望能今年晚些时候可以测试疫苗。

然而,疫苗实验是非常费钱和复杂的,失败率也相当高。一项可控的传染研究可以充当守门人的角色,Roestenberg说,“它会给出指示,这在人体身上到底有效还是无效。”

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    2018-02-25 jichang
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    2018-02-25 ylz8404
  4. [GetPortalCommentsPageByObjectIdResponse(id=1907085, encodeId=5b11190e085e0, content=<a href='/topic/show?id=4fe55200691' target=_blank style='color:#2F92EE;'>#志愿者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=52006, encryptionId=4fe55200691, topicName=志愿者)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8fc0211, createdName=doctor-chen9582, createdTime=Fri Oct 05 10:20:00 CST 2018, time=2018-10-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1375769, encodeId=141f13e576914, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Sun Feb 25 23:20:00 CST 2018, time=2018-02-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1428867, encodeId=4e1b142886e4c, content=<a href='/topic/show?id=ce5a8898902' target=_blank style='color:#2F92EE;'>#血吸虫#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88989, encryptionId=ce5a8898902, topicName=血吸虫)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=38144138896, createdName=ylz8404, createdTime=Sun Feb 25 23:20:00 CST 2018, time=2018-02-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=290468, encodeId=7f1f29046803, content=学习了.涨知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Sat Feb 24 09:16:04 CST 2018, time=2018-02-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=290461, encodeId=7d712904612c, content=学习谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4Nd44v3xHnnictn9UpctwtH62EPQ59TMdI9lnqHMgQ16nH7GmGCfpzicsHgjibYVk6vwSpXrC86gMibRkoaIzf5HwSz7/0, createdBy=78cc1691107, createdName=龙胆草, createdTime=Sat Feb 24 08:59:15 CST 2018, time=2018-02-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=290441, encodeId=50b8290441fb, content=一起学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/TDiaAWyicHgedzX3wKo3qcxudVJib7AfibfvNeufHRF2jG3Bw8MmZyWjIhtBV1mpJI7Sy9n7RcBKK5t3CuOKuOFxkg/0, createdBy=dd702206933, createdName=wzb521zf, createdTime=Sat Feb 24 08:28:50 CST 2018, time=2018-02-24, status=1, ipAttribution=)]
    2018-02-24 1ddf0692m34(暂无匿称)

    学习了.涨知识

    0

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    2018-02-24 龙胆草

    学习谢谢分享

    0

  6. [GetPortalCommentsPageByObjectIdResponse(id=1907085, encodeId=5b11190e085e0, content=<a href='/topic/show?id=4fe55200691' target=_blank style='color:#2F92EE;'>#志愿者#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=51, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=52006, encryptionId=4fe55200691, topicName=志愿者)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=8fc0211, createdName=doctor-chen9582, createdTime=Fri Oct 05 10:20:00 CST 2018, time=2018-10-05, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1375769, encodeId=141f13e576914, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Sun Feb 25 23:20:00 CST 2018, time=2018-02-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1428867, encodeId=4e1b142886e4c, content=<a href='/topic/show?id=ce5a8898902' target=_blank style='color:#2F92EE;'>#血吸虫#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=88989, encryptionId=ce5a8898902, topicName=血吸虫)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=38144138896, createdName=ylz8404, createdTime=Sun Feb 25 23:20:00 CST 2018, time=2018-02-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=290468, encodeId=7f1f29046803, content=学习了.涨知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=61, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220115/46bcf39c32de4aa6b45c5f9d66c8ee77/6cb4a20c55bb4b7691122f47747bfca2.jpg, createdBy=9dad1662329, createdName=1ddf0692m34(暂无匿称), createdTime=Sat Feb 24 09:16:04 CST 2018, time=2018-02-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=290461, encodeId=7d712904612c, content=学习谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=73, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4Nd44v3xHnnictn9UpctwtH62EPQ59TMdI9lnqHMgQ16nH7GmGCfpzicsHgjibYVk6vwSpXrC86gMibRkoaIzf5HwSz7/0, createdBy=78cc1691107, createdName=龙胆草, createdTime=Sat Feb 24 08:59:15 CST 2018, time=2018-02-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=290441, encodeId=50b8290441fb, content=一起学习学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=77, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/TDiaAWyicHgedzX3wKo3qcxudVJib7AfibfvNeufHRF2jG3Bw8MmZyWjIhtBV1mpJI7Sy9n7RcBKK5t3CuOKuOFxkg/0, createdBy=dd702206933, createdName=wzb521zf, createdTime=Sat Feb 24 08:28:50 CST 2018, time=2018-02-24, status=1, ipAttribution=)]
    2018-02-24 wzb521zf

    一起学习学习

    0

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