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与不同载体融合的抗原的表达及其作为疫苗的有效性。

Expression of Antigens Fused to Different Vectors and Their Effectiveness as Vaccines.

作者信息

Xu Han, Huang Jing, Liu Zhaolu, Li Xin, Wang Kangfeng, Feng Erling, Wu Jun, Zhu Li, Yao Kaihu, Pan Chao, Wang Hengliang

机构信息

State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, 20 Dongdajie Street, Fengtai District, Beijing 100071, China.

Beijing Children's Hospital Affiliated to Capital University of Medical Sciences, Nan Lishi Road, Xicheng District, Beijing 100045, China.

出版信息

Vaccines (Basel). 2021 May 21;9(6):542. doi: 10.3390/vaccines9060542.

Abstract

Pertussis is an acute respiratory tract infection caused by . Even though its current vaccine coverage is relatively broad, they still have some shortcomings such as short protection time and might be incapable of blocking the spread of the disease. In this study, we developed new pertussis vaccine candidates by separately fusing three pertussis antigens ( fimbriae 2 "Fim2", pertussis toxin S1 subunit "PtxS1", and filamentous hemagglutinin "FHA") to each of two immune-boosting carrier proteins (B subunits of AB5 toxin family: cholera toxin B subunit "CTB" and shiga toxin B subunit "StxB"). We then immunized mice with these fusion antigens and found that they significantly increased the serum antibody titers and elicited high bactericidal activity against . After CTB-or StxB-fused antigen-immunized mice were challenged with a non-lethal dose of , the bacterial loads in different tissues of these mice were significantly reduced, and their lung damage was nearly invisible. Furthermore, we also demonstrated that these candidate vaccines could provide strong prophylactic effects against a lethal challenge with . Overall, our candidate vaccines conferred better immune protection to mice compared with pertussis antigen alone. This B5 subunit-based vaccine strategy provides a promising option for vaccine design.

摘要

百日咳是一种由……引起的急性呼吸道感染。尽管其目前的疫苗接种覆盖率相对较广,但仍存在一些缺点,如保护时间短,可能无法阻止疾病传播。在本研究中,我们通过将三种百日咳抗原(菌毛2“Fim2”、百日咳毒素S1亚基“PtxS1”和丝状血凝素“FHA”)分别与两种免疫增强载体蛋白(AB5毒素家族的B亚基:霍乱毒素B亚基“CTB”和志贺毒素B亚基“StxB”)融合,开发了新的百日咳疫苗候选物。然后我们用这些融合抗原免疫小鼠,发现它们显著提高了血清抗体滴度,并引发了对……的高杀菌活性。用CTB或StxB融合抗原免疫的小鼠经非致死剂量的……攻击后,这些小鼠不同组织中的细菌载量显著降低,且其肺部损伤几乎不可见。此外,我们还证明了这些候选疫苗可以对……的致死性攻击提供强大的预防作用。总体而言,与单独的百日咳抗原相比,我们的候选疫苗为小鼠提供了更好的免疫保护。这种基于B5亚基的疫苗策略为疫苗设计提供了一个有前景的选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0361/8224380/a7e127f3862d/vaccines-09-00542-g001.jpg

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