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新型DNA疫苗经减毒鼠伤寒沙门氏菌递送可诱导免疫反应并提供针对鸭肠炎病毒的保护。

Attenuated Salmonella Typhimurium delivery of a novel DNA vaccine induces immune responses and provides protection against duck enteritis virus.

作者信息

Liu Xueyan, Liu Qing, Xiao Kangpeng, Li Pei, Liu Qiong, Zhao Xinxin, Kong Qingke

机构信息

Institute of Preventive Veterinary Medicine, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China.

Department of Bioengineering, College of Veterinary Medicine, Sichuan Agricultural University, Chengdu, Sichuan 611130, China.

出版信息

Vet Microbiol. 2016 Apr 15;186:189-98. doi: 10.1016/j.vetmic.2016.03.001. Epub 2016 Mar 5.

DOI:10.1016/j.vetmic.2016.03.001
PMID:27016773
Abstract

DNA vaccines are widely used to prevent and treat infectious diseases, cancer and autoimmune diseases; however, their relatively low immunogenicity is an obstacle to their use. In this study, we constructed a novel and universal DNA vaccine vector (pSS898) that can be used to build DNA vaccines against duck enteritis virus (DEV) and other viruses that require DNA vaccines to provide protection. This vaccine vector has many advantages, including innate immunogenicity, efficient nuclear trafficking and resistance to attack from nucleases. UL24 and tgB from DEV were chosen as the antigens, and the heat labile enterotoxin B subunit (LTB) from Escherichia coli and the IL-2 gene (DuIL-2) from duck were used as adjuvants for the construction of DNA vaccine plasmids. Ducklings that were orally immunized with S739 (Salmonella Typhimurium Δasd-66 Δcrp-24 Δcya-25) and harboring these DEV DNA vaccines produced strong mucosal and systemic immune responses, and they resisted an otherwise lethal DEV challenge. More importantly, S739 (UL24-LTB) provided 90% protection after a priming-boost immunization. This study shows that our novel and universal DNA vaccine vector can be used efficiently in practical applications and may provide a promising method of orally inoculating ducks with a DEV DNA vaccine delivered by attenuated Salmonella Typhimurium for prevention of DVE.

摘要

DNA疫苗被广泛用于预防和治疗传染病、癌症及自身免疫性疾病;然而,其相对较低的免疫原性是其应用的一个障碍。在本研究中,我们构建了一种新型通用DNA疫苗载体(pSS898),可用于构建针对鸭肠炎病毒(DEV)及其他需要DNA疫苗提供保护的病毒的DNA疫苗。该疫苗载体具有诸多优势,包括固有免疫原性、高效的核转运能力以及对核酸酶攻击的抗性。选取DEV的UL24和tgB作为抗原,并将来自大肠杆菌的热不稳定肠毒素B亚基(LTB)和来自鸭的IL-2基因(DuIL-2)用作佐剂来构建DNA疫苗质粒。用携带这些DEV DNA疫苗的S739(鼠伤寒沙门氏菌Δasd - 66Δcrp - 24Δcya - 25)口服免疫雏鸭,可产生强烈的黏膜和全身免疫反应,并且它们能抵抗原本致命的DEV攻击。更重要的是,经初次免疫 - 加强免疫后,S739(UL24 - LTB)提供了90%的保护率。本研究表明,我们的新型通用DNA疫苗载体可在实际应用中高效使用,并且可能为通过减毒鼠伤寒沙门氏菌递送DEV DNA疫苗口服接种鸭预防鸭病毒性肠炎提供一种有前景的方法。

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