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鼻腔免疫共生菌可提供针对肺炎链球菌肺部感染的保护免疫。

Intranasal Immunization with the Commensal Confers Protective Immunity against Pneumococcal Lung Infection.

机构信息

Institute of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway

Institute of Oral Biology, Faculty of Dentistry, University of Oslo, Oslo, Norway.

出版信息

Appl Environ Microbiol. 2019 Mar 6;85(6). doi: 10.1128/AEM.02235-18. Print 2019 Mar 15.


DOI:10.1128/AEM.02235-18
PMID:30683742
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6414371/
Abstract

is a bacterial pathogen that causes various diseases of public health concern worldwide. Current pneumococcal vaccines target the capsular polysaccharide surrounding the cells. However, only up to 13 of more than 90 pneumococcal capsular serotypes are represented in the current conjugate vaccines. In this study, we used two experimental approaches to evaluate the potential of , a commensal that exhibits immune cross-reactivity with , to confer protective immunity to lung infection in mice. First, we assessed the immune response and protective effect of wild-type against lung infection by strains D39 (serotype 2) and TIGR4 (serotype 4). Second, we examined the ability of an mutant expressing the type 4 capsule ( TIGR4cps) to elicit focused protection against TIGR4. Our results showed that intranasal immunization of mice with produced significantly higher levels of serum IgG and IgA antibodies reactive to both and , as well as enhanced production of interleukin 17A (IL-17A), but not gamma interferon (IFN-γ) and IL-4, compared with control mice. The immunization resulted in a reduced bacterial load in respiratory tissues following lung infection with TIGR4 or D39 compared with control mice. With TIGR4cps, protection upon challenge with TIGR4 was superior. Thus, these findings show the potential of to elicit natural serotype-independent protection against two pneumococcal serotypes and to provide the benefits of the well-recognized protective effect of capsule-targeting vaccines. causes various diseases worldwide. Current pneumococcal vaccines protect against a limited number of more than 90 pneumococcal serotypes, accentuating the urgent need to develop novel prophylactic strategies. and the commensal share immunogenic characteristics that make an attractive vaccine candidate against In this study, we evaluated the potential of and its mutant expressing pneumococcal capsule type 4 ( TIGR4cps) to induce protection against lung infection in mice. Our findings show that intranasal vaccination with protects against strains D39 (serotype 2) and TIGR4 (serotype 4) in a serotype-independent fashion, which is associated with enhanced antibody and T cell responses. Furthermore, TIGR4cps conferred additional protection against TIGR4, but not against D39. The findings highlight the potential of to generate protection that combines both serotype-independent and serotype-specific responses.

摘要

是一种细菌病原体,可导致全球公共卫生关注的各种疾病。目前的肺炎球菌疫苗针对细胞周围的荚膜多糖。然而,目前的结合疫苗仅能代表超过 90 种肺炎球菌荚膜血清型中的 13 种。在这项研究中,我们使用了两种实验方法来评估 ,一种与 表现出免疫交叉反应的共生菌,在小鼠肺部感染中提供保护免疫的潜力。首先,我们评估了野生型 对肺炎球菌菌株 D39(血清型 2)和 TIGR4(血清型 4)肺部感染的免疫反应和保护作用。其次,我们研究了表达 4 型荚膜(TIGR4cps)的 突变体引发针对 TIGR4 的集中保护的能力。我们的结果表明,与对照组小鼠相比,经鼻腔免疫接种小鼠可产生针对 和 的血清 IgG 和 IgA 抗体反应水平显著升高,以及白细胞介素 17A(IL-17A)的产生增强,但γ干扰素(IFN-γ)和 IL-4 没有增强。与对照组小鼠相比,肺部感染 TIGR4 或 D39 后,呼吸道组织中的细菌负荷减少。用 TIGR4cps 免疫接种,在挑战 TIGR4 时提供了更好的保护。因此,这些发现表明 有潜力引发针对两种肺炎球菌血清型的天然非血清型依赖性保护,并提供针对胶囊靶向疫苗的公认保护作用的益处。在全球范围内引起多种疾病。目前的肺炎球菌疫苗可预防超过 90 种肺炎球菌血清型中的有限数量,突出了迫切需要开发新的预防性策略。 和共生菌 具有免疫原性特征,使 成为针对 的有吸引力的疫苗候选物。在这项研究中,我们评估了 和表达肺炎球菌 4 型荚膜(TIGR4cps)的突变体在诱导小鼠肺部感染保护中的潜力。我们的发现表明,鼻腔内接种 可非血清型依赖方式保护小鼠免受 菌株 D39(血清型 2)和 TIGR4(血清型 4)的侵害,这与增强的抗体和 T 细胞反应有关。此外, TIGR4cps 提供了针对 TIGR4 的额外保护,但不能针对 D39。这些发现强调了 产生结合非血清型和血清型特异性反应的保护的潜力。

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Intranasal Immunization with the Commensal Confers Protective Immunity against Pneumococcal Lung Infection.

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本文引用的文献

[1]
Antibodies Reactive to Commensal Show Cross-Reactivity With Virulent Serotypes.

Front Immunol. 2018-4-16

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Nat Rev Immunol. 2017-1

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A Review of Pneumococcal Vaccines: Current Polysaccharide Vaccine Recommendations and Future Protein Antigens.

J Pediatr Pharmacol Ther. 2016

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