Eur Heart J:新型疫苗能降胆固醇,未来降脂手段可能会更加丰富!

2017-07-13 佚名 嘉音

6月19日,在线发表于《Eur Heart J》杂志的一项研究显示,一类用于降脂的疫苗类药物在小鼠水平的试验结果良好,目前正准备进行Ⅰ期临床试验。 根据疾病控制和预防中心(CDC)数据,美国大约有7350万成年人低密度脂蛋白胆固醇(LDL-C)偏高。高LDL-C的患者发生心脏病的可能性是LDL-C较低者的2倍。研究证实通过生活方式的改变可以帮助降低LDL-C水平,但部分患者仍需要用药。

6月19日,在线发表于《Eur Heart J》杂志的一项研究显示,一类用于降脂的疫苗类药物在小鼠水平的试验结果良好,目前正准备进行Ⅰ期临床试验。

根据疾病控制和预防中心(CDC)数据,美国大约有7350万成年人低密度脂蛋白胆固醇(LDL-C)偏高。高LDL-C的患者发生心脏病的可能性是LDL-C较低者的2倍。研究证实通过生活方式的改变可以帮助降低LDL-C水平,但部分患者仍需要用药。

靶向PCSK9酶的疫苗

前蛋白转化酶枯草杆菌蛋白酶Kexin9型(PCSK9),目前已经成为高胆固醇血症和动脉粥样硬化新的治疗靶点。由肝脏产生的PCSK9,可与LDL-C受体结合,使LDL-C的被清除率降低,升高血清LDL-C水平而增加动脉粥样硬化风险。因此,阻断PCSK9被认为是降低LDL-C的治疗策略。

在最近发表在欧洲心脏杂志的新研究中,Günther Staffler博士及其同事描述了靶向阻断PCSK9活性的疫苗的开发。该疫苗编号为AT04A,已经进入人临床试验阶段,预计到今年年底将会有结果。如果发现疫苗在人体中安全有效,研究人员说它将提供高胆固醇长期治疗策略:患者可简单地进行初次注射,随后每年只需加强注射一次即可。

研究评估了AT04A抗PCSK9疫苗在动脉粥样硬化APOE * 3Leiden.CETP小鼠模型中改善甚至预防冠心病的治疗潜力。对照组和AT04A疫苗治疗组小鼠均给予西式饮食(高脂、高糖和高胆固醇)18周。使用ELISA、FPLC和多重免疫分析分别测定抗体滴度、血脂和炎症标志物水平。通过主动脉窦连续横断面的组织学分析评估动脉粥样硬化进展。

小鼠中的总胆固醇水平下降一半

Staffler博士和研究小组透露,AT04A疫苗注射后会产生针对PCSK9的抗体,并阻止其发挥作用。这增加了LDL受体活性,使它们能够从血液中清除LDL-C。研究人员在高脂饮食诱导具有高LDL-C和动脉粥样硬化的小鼠中测试了疫苗的作用。

与对照组相比,AT04A疫苗组小鼠有持续的高PCSK9抗体水平,血浆总胆固醇(-53%,P<0.001)和LDL-C水平显着降低。AT04A治疗组小鼠的血浆炎症标志物如血清淀粉样蛋白A(SAA)、巨噬细胞炎症蛋白-1β(MIP-1β/CCL4)、巨噬细胞源趋化因子(MDC/CCL22)、细胞因子的干细胞因子(SCF)和血管内皮生长因子A(VEGF-A)水平均显着降低。

研究小组发现,与未接种疫苗的小鼠相比,AT04A疫苗接种组小鼠的总胆固醇水平降低了53%,动脉粥样硬化相关血管损伤减少了64%。此外,疫苗可使血管炎症生物标志物水平降低21%~28%。

重要的是,研究人员发现疫苗产生的抗体在整个18周研究期间保持高效功能,这表明它具有长期获益。“研究结束时抗体浓度依然很高,可认为它们会在一段时间后继续降低胆固醇水平,从而产生持久疗效”Staffler说。

结论指出,AT04A疫苗在APOE * 3Leiden.CETP小鼠中诱导了针对PCSK9的有效免疫应答,导致血脂水平显着降低,减轻全身和血管炎症以及主动脉中的动脉粥样硬化病变的发生。

人临床试验已经开始

基于AT04A在小鼠研究中的成功,疫苗的I期临床试验已经于2015年开始,共纳入72名健康成年人。该研究将在今年年底前完成。

“如果这些结果在人身上成功转化,这可能意味着诱导的抗体在接种后数月持续。因此,我们可以开发一种持久治疗方法,在首次接种疫苗后只需要1年一次的加强注射。这将为患者提供一种更有效和更方便的治疗方法,以及提高患者依从性。”Staffler说。

虽然AT04A疫苗显示出希望,但研究人员强调确定该治疗策略的长期安全性非常重要。德国Saarland大学Ulrich Laufs教授和英国Bristol大学Brian Ference教授在该研究的评述中写道:“通过他汀和其他药物降低总胆固醇可能与新发糖尿病有关,因此,针对PCSK9疫苗长期降低LDL-C的一个潜在安全性问题是其是否也同样有增加新发糖尿病的风险。”“但目前,他汀和PCSK9抑制剂降低LDL-C的获益仍远远超过新发糖尿病的风险。”他们补充说道。
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    2020-06-24 148ccaa6m02暂无昵称

    真的是价格一年一万可以接受,一年十万就难了

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    2017-07-20 1e1b8c04m38(暂无匿称)

    学习

    0

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    2017-07-17 lou.minghong

    的确值得探索!

    0

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    2017-07-14 zhaojie88
  5. [GetPortalCommentsPageByObjectIdResponse(id=799626, encodeId=01d7e99626c4, content=真的是价格一年一万可以接受,一年十万就难了, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=bf435331051, createdName=148ccaa6m02暂无昵称, createdTime=Wed Jun 24 23:13:12 CST 2020, time=2020-06-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=224187, encodeId=a63f22418ee9, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://cacheapi.medsci.cn/resource/upload/20161217/IMG585499DFC35A96490.jpg, createdBy=72381996390, createdName=1e1b8c04m38(暂无匿称), createdTime=Thu Jul 20 09:17:22 CST 2017, time=2017-07-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=223006, encodeId=9f7c22300670, content=的确值得探索!, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/oLAjfB7s1ib2JlGvwpAibiaovVhfA9DbO7X7JLGGjM4Cic6oMgxLdnuS9piaP9cnG2OwIbkzHvX0qzS1boibyYNqR5vHZu7HQs5EIB/0, createdBy=298d1398341, createdName=lou.minghong, createdTime=Mon Jul 17 03:44:07 CST 2017, time=2017-07-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1356411, encodeId=9cd21356411e1, content=<a href='/topic/show?id=b0702e84b9' target=_blank style='color:#2F92EE;'>#ART#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2784, encryptionId=b0702e84b9, topicName=ART)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=zhaojie88, createdTime=Fri Jul 14 23:10:00 CST 2017, time=2017-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1562627, encodeId=20fb156262e17, content=<a href='/topic/show?id=f69d864413' target=_blank style='color:#2F92EE;'>#HEART#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=8644, encryptionId=f69d864413, topicName=HEART)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=80d715270048, createdName=slcumt, createdTime=Fri Jul 14 23:10:00 CST 2017, time=2017-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=222245, encodeId=256a222245d7, content=新方法降胆固醇。, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=60791943465, createdName=1e0f8808m18(暂无匿称), createdTime=Fri Jul 14 14:45:59 CST 2017, time=2017-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=222155, encodeId=b5dd222155a2, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=98dd1959726, createdName=游手好闲, createdTime=Fri Jul 14 09:13:57 CST 2017, time=2017-07-14, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=221824, encodeId=de7122182419, content=学习了/,谢谢分享。, beContent=null, objectType=article, channel=null, level=null, likeNumber=23, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=60791943465, createdName=1e0f8808m18(暂无匿称), createdTime=Thu Jul 13 11:10:01 CST 2017, time=2017-07-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=221822, encodeId=6cc1221822e2, content=谢谢分享受益匪浅, beContent=null, objectType=article, channel=null, level=null, likeNumber=18, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6ae02063908, createdName=152****8376, createdTime=Thu Jul 13 11:02:56 CST 2017, time=2017-07-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=221753, encodeId=447d221e5346, content=签到学习了很多。, beContent=null, objectType=article, channel=null, level=null, likeNumber=17, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://q.qlogo.cn/qqapp/1103841572/A3E53E62691178E2F18D7B999FD22131/100, createdBy=f44d2003846, createdName=Chongyang Zhang, createdTime=Thu Jul 13 09:27:29 CST 2017, time=2017-07-13, status=1, ipAttribution=)]
    2017-07-14 slcumt
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    2017-07-14 1e0f8808m18(暂无匿称)

    新方法降胆固醇。

    0

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    2017-07-14 游手好闲

    学习了

    0

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    2017-07-13 1e0f8808m18(暂无匿称)

    学习了/,谢谢分享。

    0

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    2017-07-13 152****8376

    谢谢分享受益匪浅

    0

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    2017-07-13 Chongyang Zhang

    签到学习了很多。

    0

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2016年4月起,在全球范围内,三价口服脊髓灰质炎疫苗(tOPV)被二价I型和3型口服脊髓灰质炎疫苗(bOPV)和一剂量的灭活脊髓灰质炎病毒(IPV)所取代。对于这一改变后II型脊髓灰质炎病毒或Sabin2病毒(脊髓灰质炎病毒的一种)对于II型脊髓灰质炎的再次引入或发生的传播风险尚未完全清楚。

npj Vaccines:基于DNA新的策略,对流感病毒的治疗显示出希望

Wistar研究所MedImmune和Inovio Pharmaceuticals公司的科学家在临床前模型中开发了一种新颖、合成的基于DNA的策略,来提供针对各种流感病毒的保护。这些研究结果强调了这一有前景的策略,发表在npj疫苗上。

Nature:个性化新抗原疫苗引发强烈抗肿瘤反应,攻克癌症治疗两大障碍!

Dana-Farber癌症研究所和麻省理工学院广泛研究所的研究已经显示靶向肿瘤细胞上特征性的“新抗原”的个体癌症治疗疫苗可刺激黑素瘤患者的有效,安全和高度特异性的免疫抗肿瘤反应。