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一种在表面展示炭疽抗原的鼻用疫苗可诱导针对炭疽毒素的保护性黏膜免疫。

A Nasal Vaccine Displaying Anthrax Antigen on the Surface of Induces Protective Mucosal Immunity against Anthrax Toxin.

作者信息

Jang In-Hwan, Jung In Ryeong, Suh Hyojung, Ahn Hyo-Joo, Kim Donghyun, Choi Youn Soo, Lee June-Yong, Lee Kyung-Ah

机构信息

Department of Microbiology & Immunology, Seoul National University College of Medicine, Seoul 03080, Republic of Korea.

Department of Microbiology and Immunology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.

出版信息

J Microbiol Biotechnol. 2025 May 26;35:e2503036. doi: 10.4014/jmb.2503.03036.

DOI:10.4014/jmb.2503.03036
PMID:40443240
Abstract

Anthrax, particularly inhalational anthrax, poses a severe threat due to its high fatality rate and potential misuse as a biological weapon. Current anthrax vaccines require multiple injections, which limits their practicality and underscores the need for improved, user-friendly vaccination strategies. In this study, we developed a novel nasal booster vaccine platform aimed at preventing inhalational anthrax by inducing mucosal immunity at the pathogen's entry site, the respiratory tract. We successfully engineered a biologically safe () strain to display the anthrax protective antigen (PA) on its surface. Following systemic priming by intramuscular immunization, nasal boosting with this recombinant strain significantly enhanced protective antigen (PA)-specific mucosal IgA production in both nasal and bronchoalveolar lavage fluids. Importantly, mucosal IgA antibodies elicited through this nasal boosting strategy effectively neutralized anthrax lethal toxin. Our findings indicate that recombinant expressing PA represents a promising nasal vaccine booster platform, potentially replacing traditional intramuscular boosters, and paving the way for the development of effective and easily administered mucosal vaccines against anthrax and other respiratory pathogens.

摘要

炭疽,尤其是吸入性炭疽,因其高致死率以及作为生物武器被潜在滥用的可能性而构成严重威胁。当前的炭疽疫苗需要多次注射,这限制了它们的实用性,并凸显了改进的、用户友好型疫苗接种策略的必要性。在本研究中,我们开发了一种新型鼻内加强疫苗平台,旨在通过在病原体进入部位呼吸道诱导黏膜免疫来预防吸入性炭疽。我们成功改造了一种生物安全的()菌株,使其在表面展示炭疽保护性抗原(PA)。在通过肌肉注射进行全身初次免疫后,用这种重组菌株进行鼻内加强免疫显著增强了鼻腔和支气管肺泡灌洗液中保护性抗原(PA)特异性黏膜IgA的产生。重要的是,通过这种鼻内加强免疫策略产生的黏膜IgA抗体有效中和了炭疽致死毒素。我们的研究结果表明,表达PA的重组()代表了一个有前景的鼻内疫苗加强平台,有可能取代传统的肌肉注射加强针,并为开发针对炭疽和其他呼吸道病原体的有效且易于给药的黏膜疫苗铺平道路。

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Unadjuvanted intranasal spike vaccine elicits protective mucosal immunity against sarbecoviruses.未佐剂化鼻内刺突疫苗引发针对沙贝科病毒的保护性黏膜免疫。
Science. 2022 Nov 25;378(6622):eabo2523. doi: 10.1126/science.abo2523.
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Protective mucosal immunity against SARS-CoV-2 after heterologous systemic prime-mucosal boost immunization.异源系统初级-黏膜加强免疫后对 SARS-CoV-2 的保护性黏膜免疫。
Nat Commun. 2021 Nov 26;12(1):6871. doi: 10.1038/s41467-021-27063-4.
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Probiotic-Based Vaccines May Provide Effective Protection against COVID-19 Acute Respiratory Disease.基于益生菌的疫苗可能为预防新冠急性呼吸道疾病提供有效保护。
Vaccines (Basel). 2021 May 6;9(5):466. doi: 10.3390/vaccines9050466.
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Does anthrax antitoxin therapy have a role in the treatment of inhalational anthrax?抗炭疽毒素治疗在吸入性炭疽的治疗中有作用吗?
Curr Opin Infect Dis. 2018 Jun;31(3):257-262. doi: 10.1097/QCO.0000000000000446.
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