Science Translational Medicine:口服新冠疫苗,在第一道防线发挥保护作用,降低空气传播

2022-05-10 王聪 “生物世界”公众号

导致疫苗犹豫的原因有很多,其中一种重要原因是有不少人害怕针头注射,因此,口服疫苗能够克服这一部分人群的疫苗犹豫问题。此外,口服疫苗除了可以产生全身性抗体反应,还能引起粘膜免疫。

在全世界范围内,有很多国家和地区的新冠疫苗接种率仍然不足,尤其是儿童和老人。而随着新冠疫苗变异株的不断出现,接种疫苗后的突破性感染者也越来越多,他们会导致进一步社区传播,从而造成公共卫生风险。因此,开发同时具有预防感染和减少对未接6种疫苗人群传播的疫苗,对于控制疫情发展,结束大流行非常重要。

导致疫苗犹豫的原因有很多,其中一种重要原因是有不少人害怕针头注射,因此,口服疫苗能够克服这一部分人群的疫苗犹豫问题。此外,口服疫苗除了可以产生全身性抗体反应,还能引起粘膜免疫,从而增强人体免疫系统抵抗病原体的第一道防线,这样一来,就能在发生突破性感染时减少因打喷嚏、咳嗽及呼吸时导致的空气传播。

美国疫苗公司 Vaxart ,是一家致力于开发口服疫苗的临床阶段生物公司,他们有两款基于腺病毒5型的口服新冠候选疫苗,分别处于临床1期和临床2期阶段。

近日,Vaxart 公司和杜克大学的科学家合作,在 Science 子刊 Science Translational Medicine 发表了题为:Adenovirus type 5 SARS-CoV-2 vaccines delivered orally or intranasally reduced disease severity and transmission in a hamster model 的研究论文。

这项针对仓鼠的动物实验显示,基于腺病毒5型的口服新冠候选疫苗,会在血液和肺部引起强烈的抗体反应。当它们暴露于高水平的新冠病毒并引发突破性感染时,症状要比未接种疫苗的仓鼠轻微,且鼻腔和肺部的新冠病毒量显着减少。

使用同一平台的编码新冠病毒刺突蛋白+核衣壳蛋白(S+N)的口服新冠病毒候选疫苗的1期临床数据显示,其能够诱导粘膜免疫,增加免疫球蛋白A(IgA)的产生。

这些结果表明,这款口服新冠候选疫苗不仅可以预防新冠病毒感染和疾病严重程度,还能减少新冠病毒通过空气传播给其他密切接触者

该论文的共同通讯作者、杜克大学的 Stephanie Langel 研究员表示,与注射到肌肉的疫苗不同,口服或鼻腔吸入的疫苗,还会通过粘膜免疫增加免疫球蛋白A(IgA)的产生,从而增强免疫系统抵抗病原体的第一道防线。这些接种者即使突破性感染,也不太可能在打喷嚏或咳嗽时传播病毒。

口服或鼻腔吸入减少了新冠病毒的空气传播

该研究还对35名健康人进行了该口服疫苗的1期临床实验(NCT04563702),其中15人接受单剂低剂量口服(1×1010 IU),15人接受单剂高剂量口服(5×1010 IU),5人接受两剂低剂量口服(2×1×1010 IU)。54% (19/35) 的口服疫苗接种者在唾液或鼻腔样本中的黏膜 IgA 增加了2倍或更高。

研究团队还表示,口服的、温度稳定的新冠疫苗是全球新冠疫苗接种运动的理想选择。鼻腔吸入疫苗具有类似的优势,但事实证明,在人类中转化的鼻腔吸入式新冠疫苗的效力低于之前的动物实验数据。而已在世界各地广泛接种的轮状病毒和脊髓灰质炎病毒的口服疫苗证实了这种疫苗接种方式的可行性。研究团队此前的动物实验和正在进行的两项人体临床试验证实了口服新冠疫苗良好的安全性和免疫原性。此次的实验数据则进一步说明,口服新冠疫苗还可以通过粘膜免疫减少新冠病毒的空气传播,也表明粘膜免疫是减少新冠病毒通过空气传播的可行策略。

Vaxart 公司的口服疫苗采用其自主产权的 VAAST? 递送平台,这是一种模块化平台,使用无复制能力的腺病毒5型(Ad5)作为递送载体,携带两种有效成分——抗原(Antigen)和TLR3佐剂,以口服片剂的形式,递送至小肠黏膜上皮细胞。这种片剂形式的口服疫苗,除了给药方便,还可在25℃的室温下稳定保存。

Vaxart 公司目前有两款口服新冠疫苗正在临床试验中,一种是表达新冠病毒的刺突蛋白(S),目前处于2期临床;另一种是表达新冠病毒的刺突蛋白+核衣壳蛋白(S+N),目前已完成1期临床。

Vaxart 公司研发管线

Vaxart 公司目前共有5条研发管线,分为预防性疫苗和治疗性疫苗,预防性疫苗有4种,分别是诺如病毒疫苗、流感疫苗、呼吸道合胞病毒疫苗,以及新冠疫苗,其中新冠疫苗分两种。

治疗性疫苗1种,为 HPV 疫苗,用于治疗由 HPV16 和 HPV18 感染导致的宫颈发育不良和癌症,目前还处于临床前阶段。小鼠模型实验显示,这款 HPV 疫苗能够引发 T 细胞免疫并促进活化 T 细胞进入肿瘤组织中,导致肿瘤细胞死亡,显着减小肿瘤体积。

原始出处:

STEPHANIE N. LANGEL, et al. Adenovirus type 5 SARS-CoV-2 vaccines delivered orally or intranasally reduced disease severity and transmission in a hamster model. SCIENCE TRANSLATIONAL MEDICINE, 5 May 2022.

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channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75356, encryptionId=08fce5356f2, topicName=空气传播)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=872f168, createdName=gracezdd, createdTime=Thu Jan 12 17:37:09 CST 2023, time=2023-01-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1795955, encodeId=80861e95955d2, content=<a href='/topic/show?id=42211e757d7' target=_blank style='color:#2F92EE;'>#Translation#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17757, encryptionId=42211e757d7, topicName=Translation)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eqPdWFricgmt6Dde2ptNxJzD6Y9c4cxpXdTo4pNlVPARAnFdKu6nWIPele9icxApTaFgibq0uVlgRiceQ/132, createdBy=4b8c2500026, createdName=ms8435843352634314, createdTime=Tue Nov 15 13:37:09 CST 2022, time=2022-11-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1859257, encodeId=c217185925ebc, content=<a href='/topic/show?id=e0a9593596' target=_blank style='color:#2F92EE;'>#DIC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5935, encryptionId=e0a9593596, topicName=DIC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6f7770, createdName=jeanqiuqiu, createdTime=Wed Feb 08 00:37:09 CST 2023, time=2023-02-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1774055, encodeId=1fd01e74055be, content=<a href='/topic/show?id=5f014e1852' target=_blank style='color:#2F92EE;'>#CIN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4718, encryptionId=5f014e1852, topicName=CIN)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a9a038523631, createdName=kalseyzl, createdTime=Wed Feb 08 20:37:09 CST 2023, time=2023-02-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1376446, encodeId=daca13e6446f6, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Wed May 11 08:37:09 CST 2022, time=2022-05-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1577893, encodeId=654215e789343, content=<a href='/topic/show?id=cda91148004' target=_blank style='color:#2F92EE;'>#Medicine#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11480, encryptionId=cda91148004, topicName=Medicine)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=54cd16396700, createdName=ms1692212821629096, createdTime=Wed May 11 08:37:09 CST 2022, time=2022-05-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1599185, encodeId=002715991850e, content=<a href='/topic/show?id=f14d2e187ac' target=_blank style='color:#2F92EE;'>#保护作用#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27187, encryptionId=f14d2e187ac, topicName=保护作用)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2ee918684940, createdName=photoman, createdTime=Wed May 11 08:37:09 CST 2022, time=2022-05-11, status=1, ipAttribution=)]
    2023-03-04 bsmagic9140
  4. 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  5. 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13:37:09 CST 2022, time=2022-11-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1859257, encodeId=c217185925ebc, content=<a href='/topic/show?id=e0a9593596' target=_blank style='color:#2F92EE;'>#DIC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5935, encryptionId=e0a9593596, topicName=DIC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6f7770, createdName=jeanqiuqiu, createdTime=Wed Feb 08 00:37:09 CST 2023, time=2023-02-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1774055, encodeId=1fd01e74055be, content=<a href='/topic/show?id=5f014e1852' target=_blank style='color:#2F92EE;'>#CIN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4718, encryptionId=5f014e1852, topicName=CIN)], attachment=null, 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  6. 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13:37:09 CST 2022, time=2022-11-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1859257, encodeId=c217185925ebc, content=<a href='/topic/show?id=e0a9593596' target=_blank style='color:#2F92EE;'>#DIC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5935, encryptionId=e0a9593596, topicName=DIC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6f7770, createdName=jeanqiuqiu, createdTime=Wed Feb 08 00:37:09 CST 2023, time=2023-02-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1774055, encodeId=1fd01e74055be, content=<a href='/topic/show?id=5f014e1852' target=_blank style='color:#2F92EE;'>#CIN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4718, encryptionId=5f014e1852, topicName=CIN)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=a9a038523631, createdName=kalseyzl, createdTime=Wed Feb 08 20:37:09 CST 2023, time=2023-02-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1376446, encodeId=daca13e6446f6, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Wed May 11 08:37:09 CST 2022, time=2022-05-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1577893, encodeId=654215e789343, content=<a href='/topic/show?id=cda91148004' target=_blank style='color:#2F92EE;'>#Medicine#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=11480, encryptionId=cda91148004, topicName=Medicine)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=54cd16396700, createdName=ms1692212821629096, createdTime=Wed May 11 08:37:09 CST 2022, time=2022-05-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1599185, encodeId=002715991850e, content=<a href='/topic/show?id=f14d2e187ac' target=_blank style='color:#2F92EE;'>#保护作用#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27187, encryptionId=f14d2e187ac, topicName=保护作用)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2ee918684940, createdName=photoman, createdTime=Wed May 11 08:37:09 CST 2022, time=2022-05-11, status=1, ipAttribution=)]
    2023-02-08 jeanqiuqiu
  7. [GetPortalCommentsPageByObjectIdResponse(id=1796077, encodeId=d60f1e9607766, content=<a href='/topic/show?id=8c201e758e5' target=_blank style='color:#2F92EE;'>#translational#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17758, encryptionId=8c201e758e5, topicName=translational)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=d81c2500028, createdName=12498561m32(暂无昵称), createdTime=Mon Aug 15 17:37:09 CST 2022, time=2022-08-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2067624, encodeId=9632206e62443, content=<a href='/topic/show?id=d0841e75535' target=_blank style='color:#2F92EE;'>#Transl#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17755, encryptionId=d0841e75535, topicName=Transl)], attachment=null, authenticateStatus=null, 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channel=null, level=null, likeNumber=37, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=75356, encryptionId=08fce5356f2, topicName=空气传播)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=872f168, createdName=gracezdd, createdTime=Thu Jan 12 17:37:09 CST 2023, time=2023-01-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1795955, encodeId=80861e95955d2, content=<a href='/topic/show?id=42211e757d7' target=_blank style='color:#2F92EE;'>#Translation#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17757, encryptionId=42211e757d7, topicName=Translation)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/DYAIOgq83eqPdWFricgmt6Dde2ptNxJzD6Y9c4cxpXdTo4pNlVPARAnFdKu6nWIPele9icxApTaFgibq0uVlgRiceQ/132, createdBy=4b8c2500026, createdName=ms8435843352634314, createdTime=Tue Nov 15 13:37:09 CST 2022, time=2022-11-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1859257, encodeId=c217185925ebc, content=<a href='/topic/show?id=e0a9593596' target=_blank style='color:#2F92EE;'>#DIC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5935, encryptionId=e0a9593596, topicName=DIC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6f7770, createdName=jeanqiuqiu, createdTime=Wed Feb 08 00:37:09 CST 2023, time=2023-02-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1774055, encodeId=1fd01e74055be, content=<a href='/topic/show?id=5f014e1852' target=_blank style='color:#2F92EE;'>#CIN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4718, encryptionId=5f014e1852, topicName=CIN)], attachment=null, 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topicName=null, topicId=null, topicList=[TopicDto(id=11480, encryptionId=cda91148004, topicName=Medicine)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=54cd16396700, createdName=ms1692212821629096, createdTime=Wed May 11 08:37:09 CST 2022, time=2022-05-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1599185, encodeId=002715991850e, content=<a href='/topic/show?id=f14d2e187ac' target=_blank style='color:#2F92EE;'>#保护作用#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27187, encryptionId=f14d2e187ac, topicName=保护作用)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2ee918684940, createdName=photoman, createdTime=Wed May 11 08:37:09 CST 2022, time=2022-05-11, status=1, ipAttribution=)]
    2023-02-08 kalseyzl
  8. 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13:37:09 CST 2022, time=2022-11-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1859257, encodeId=c217185925ebc, content=<a href='/topic/show?id=e0a9593596' target=_blank style='color:#2F92EE;'>#DIC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5935, encryptionId=e0a9593596, topicName=DIC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6f7770, createdName=jeanqiuqiu, createdTime=Wed Feb 08 00:37:09 CST 2023, time=2023-02-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1774055, encodeId=1fd01e74055be, content=<a href='/topic/show?id=5f014e1852' target=_blank style='color:#2F92EE;'>#CIN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4718, encryptionId=5f014e1852, topicName=CIN)], attachment=null, 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topicName=null, topicId=null, topicList=[TopicDto(id=11480, encryptionId=cda91148004, topicName=Medicine)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=54cd16396700, createdName=ms1692212821629096, createdTime=Wed May 11 08:37:09 CST 2022, time=2022-05-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1599185, encodeId=002715991850e, content=<a href='/topic/show?id=f14d2e187ac' target=_blank style='color:#2F92EE;'>#保护作用#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=27187, encryptionId=f14d2e187ac, topicName=保护作用)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=2ee918684940, createdName=photoman, createdTime=Wed May 11 08:37:09 CST 2022, time=2022-05-11, status=1, ipAttribution=)]
    2022-05-11 jichang
  9. 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13:37:09 CST 2022, time=2022-11-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1859257, encodeId=c217185925ebc, content=<a href='/topic/show?id=e0a9593596' target=_blank style='color:#2F92EE;'>#DIC#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=27, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5935, encryptionId=e0a9593596, topicName=DIC)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6f7770, createdName=jeanqiuqiu, createdTime=Wed Feb 08 00:37:09 CST 2023, time=2023-02-08, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1774055, encodeId=1fd01e74055be, content=<a href='/topic/show?id=5f014e1852' target=_blank style='color:#2F92EE;'>#CIN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=25, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4718, encryptionId=5f014e1852, topicName=CIN)], attachment=null, 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