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用DnaJ-ΔA146Ply进行黏膜和皮下免疫对小鼠流感和肺炎链球菌共感染的保护效力

Protective efficacy of mucosal and subcutaneous immunization with DnaJ-ΔA146Ply against influenza and Streptococcus pneumoniae co-infection in mice.

作者信息

Hu Yi, Liu Yusi, Yin Yibing, Zhang Xuemei

机构信息

Department of Laboratory Medicine, Key Laboratory of Diagnostic Medicine (Ministry of Education), Chongqing Medical University, Chongqing, 400016, China.

Department of Laboratory Medicine, The First Affiliated Hospital of China Medical University, Shenyang, 110001, China.

出版信息

Microbes Infect. 2021 Sep-Oct;23(8):104813. doi: 10.1016/j.micinf.2021.104813. Epub 2021 Mar 31.

DOI:10.1016/j.micinf.2021.104813
PMID:33798714
Abstract

Respiratory tract coinfections, specifically involving influenza A virus (IAV) and Streptococcus pneumoniae (S. pneumoniae), remain a major health problem worldwide. Secondary bacterial pneumonia is a common complication and an important cause of mortality related to seasonal and pandemic influenza infections. Vaccination is a basic control strategy against influenza and S. pneumoniae. The fusion protein DnaJ-ΔA146Ply is a vaccine candidate which can induce immune responses against pneumococcal infections via mucosal and subcutaneous immunization in mice. In the present study, we established a co-infection model using mouse-adapted laboratory strains of IAV (PR8) and S. pneumoniae (19F) in mice intranasally and subcutaneously immunized with DnaJ-ΔA146Ply. Our results showed that vaccinated mice suffered decreased weight loss compared with control mice. The survival rates were higher in intranasally and subcutaneously immunized mice than in control mice. In addition, the bacterial loads in nasal washes and lung homogenates were lower in vaccinated mice than in control mice. Furthermore, lung damage was alleviated in vaccinated mice compared with control mice, with less broken alveoli and less proinflammatory cytokine production. Taken together, these results indicate that vaccination with DnaJ-ΔA146Ply shows protective potential against influenza and S. pneumoniae co-infection in mice.

摘要

呼吸道合并感染,特别是涉及甲型流感病毒(IAV)和肺炎链球菌(S. pneumoniae)的感染,仍然是全球范围内的一个主要健康问题。继发性细菌性肺炎是季节性和大流行性流感感染常见的并发症及重要的死亡原因。接种疫苗是预防流感和肺炎链球菌的基本控制策略。融合蛋白DnaJ-ΔA146Ply是一种候选疫苗,可通过在小鼠中进行黏膜和皮下免疫来诱导针对肺炎球菌感染的免疫反应。在本研究中,我们使用适应小鼠的IAV实验室菌株(PR8)和肺炎链球菌(19F)建立了一种合并感染模型,并对小鼠进行鼻内和皮下免疫接种DnaJ-ΔA146Ply。我们的结果显示,与对照小鼠相比,接种疫苗的小鼠体重减轻减少。鼻内和皮下免疫接种的小鼠存活率高于对照小鼠。此外,接种疫苗的小鼠鼻腔冲洗液和肺匀浆中的细菌载量低于对照小鼠。此外,与对照小鼠相比,接种疫苗的小鼠肺损伤减轻,肺泡破裂减少,促炎细胞因子产生减少。综上所述,这些结果表明,用DnaJ-ΔA146Ply接种疫苗对小鼠流感和肺炎链球菌合并感染具有保护潜力。

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Protective efficacy of mucosal and subcutaneous immunization with DnaJ-ΔA146Ply against influenza and Streptococcus pneumoniae co-infection in mice.用DnaJ-ΔA146Ply进行黏膜和皮下免疫对小鼠流感和肺炎链球菌共感染的保护效力
Microbes Infect. 2021 Sep-Oct;23(8):104813. doi: 10.1016/j.micinf.2021.104813. Epub 2021 Mar 31.
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Expression of Toll-Like Receptor 2 by Dendritic Cells Is Essential for the DnaJ-ΔA146Ply-Mediated Th1 Immune Response against Streptococcus pneumoniae.树突状细胞 Toll 样受体 2 的表达对于 DnaJ-ΔA146Ply 介导的抗肺炎链球菌 Th1 免疫反应至关重要。
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Subcutaneous immunization with the fusion protein ΔA146Ply-SP0148 confers protection against Streptococcus pneumoniae infection.皮下免疫融合蛋白 ΔA146Ply-SP0148 可预防肺炎链球菌感染。
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Subcutaneous Immunization with Fusion Protein DnaJ-ΔA146Ply without Additional Adjuvants Induces both Humoral and Cellular Immunity against Pneumococcal Infection Partially Depending on TLR4.无需额外佐剂的融合蛋白DnaJ-ΔA146Ply皮下免疫可诱导针对肺炎球菌感染的体液免疫和细胞免疫,部分依赖于Toll样受体4(TLR4)。
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