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口服建模的腺病毒为基础的四价流感疫苗在雪貂和小鼠。

Oral Modeling of an Adenovirus-Based Quadrivalent Influenza Vaccine in Ferrets and Mice.

机构信息

Vaxart, Inc., South San Francisco, CA, USA.

出版信息

Infect Dis Ther. 2016 Jun;5(2):165-83. doi: 10.1007/s40121-016-0108-z. Epub 2016 Apr 12.

Abstract

INTRODUCTION

Oral vaccines delivered as tablets offer a number of advantages over traditional parenteral-based vaccines including the ease of delivery, lack of needles, no need for trained medical personnel, and the ability to formulate into temperature-stable tablets. We have been evaluating an oral vaccine platform based on recombinant adenoviral vectors for the purpose of creating a prophylactic vaccine to prevent influenza, and have demonstrated vaccine efficacy in animal models and substantial immunogenicity in humans. These studies have evaluated monovalent vaccines to date. To protect against the major circulating A and B influenza strains, a multivalent influenza vaccine will be required.

METHODS

In this study, the immunogenicity of orally delivered monovalent, bivalent, trivalent, and quadrivalent vaccines was tested in ferrets and mice. The various vaccine combinations were tested by blending monovalent recombinant adenovirus vaccines, each expressing hemagglutinin from a single strain. Human tablet delivery was modeled in animals by oral gavage in mice and by endoscopic delivery in ferrets.

RESULTS

We demonstrated minimal interference between the various vaccine vectors when used in combination and that the oral quadrivalent vaccine compared favorably to an approved trivalent inactivated vaccine.

CONCLUSION

The quadrivalent vaccine presented here produced immune responses that we predict should be capable of providing protection against multiple influenza strains, and the platform should have applications to other multivalent vaccines.

FUNDING

Vaxart, Inc.

摘要

简介

口服片剂疫苗相对于传统的基于注射的疫苗具有许多优势,包括易于给药、无需针头、无需经过培训的医务人员以及能够制成稳定的片剂。我们一直在评估基于重组腺病毒载体的口服疫苗平台,目的是开发一种预防流感的预防性疫苗,并在动物模型中证明了疫苗的功效和在人类中的显著免疫原性。这些研究迄今为止已经评估了单价疫苗。为了预防主要流行的 A 型和 B 型流感株,需要使用多价流感疫苗。

方法

在这项研究中,我们在雪貂和小鼠中测试了口服单价、双价、三价和四价疫苗的免疫原性。通过混合表达单一流感株血凝素的单价重组腺病毒疫苗来测试各种疫苗组合。通过在小鼠中进行口服灌胃和在雪貂中进行内镜给药来模拟人类片剂给药。

结果

我们证明了在组合使用时,各种疫苗载体之间的干扰最小,并且口服四价疫苗与已批准的三价灭活疫苗相比具有优势。

结论

本文提出的四价疫苗产生了我们预计能够提供针对多种流感株保护的免疫反应,该平台也应该适用于其他多价疫苗。

资助

Vaxart, Inc.

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f804/4929087/c7202df34f91/40121_2016_108_Fig1_HTML.jpg

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