基于细菌囊泡的肺炎球菌疫苗可预防流感介导的继发性肺炎链球菌肺部感染。

IF 7.9 2区 医学 Q1 IMMUNOLOGY Mucosal Immunology Pub Date : 2024-04-01 DOI:10.1016/j.mucimm.2024.01.002
Saugata Majumder , Peng Li , Shreya Das , Tanvir Noor Nafiz , Sudeep Kumar , Guangchun Bai , Hazel Dellario , Haixin Sui , Ziqiang Guan , Roy Curtiss 3rd , Yoichi Furuya , Wei Sun
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引用次数: 0

摘要

肺炎链球菌(Spn)是流感后引起继发性细菌感染的常见病原体,在季节性流感和流感大流行期间会导致严重的发病率和死亡率。因此,迫切需要开发能预防流感后重症细菌性肺炎的细菌疫苗。在本研究中,一株改良的假结核耶尔森菌(命名为 YptbS46)具有 Asd+ 质粒 pSMV92,能合成大量 Spn 肺炎球菌表面蛋白 A(PspA)抗原和作为佐剂的单磷脂 A。重组菌株能产生包裹大量 PspA 蛋白的外膜囊泡(OMV)(命名为 OMV-PspA)。用 OMV-PspA 进行肌肉注射,可诱导接种小鼠产生记忆性适应性免疫反应和先天性免疫反应,减少病毒和细菌负担,并对流感介导的 Spn 继发感染提供完全保护。此外,OMV-PspA 免疫对 Spn A66.1 的继发感染具有显著的交叉保护作用,并对 Spn D39 的继发感染具有长期保护作用。我们的研究表明,提供 Spn 抗原的 OMV 疫苗可以成为一种新的有前途的肺炎球菌候选疫苗。
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A bacterial vesicle-based pneumococcal vaccine against influenza-mediated secondary Streptococcus pneumoniae pulmonary infection

Streptococcus pneumoniae (Spn) is a common pathogen causing a secondary bacterial infection following influenza, which leads to severe morbidity and mortality during seasonal and pandemic influenza. Therefore, there is an urgent need to develop bacterial vaccines that prevent severe post-influenza bacterial pneumonia. Here, an improved Yersinia pseudotuberculosis strain (designated as YptbS46) possessing an Asd+ plasmid pSMV92 could synthesize high amounts of the Spn pneumococcal surface protein A (PspA) antigen and monophosphoryl lipid A as an adjuvant. The recombinant strain produced outer membrane vesicles (OMVs) enclosing a high amount of PspA protein (designated as OMV-PspA). A prime-boost intramuscular immunization with OMV-PspA induced both memory adaptive and innate immune responses in vaccinated mice, reduced the viral and bacterial burden, and provided complete protection against influenza-mediated secondary Spn infection. Also, the OMV-PspA immunization afforded significant cross-protection against the secondary Spn A66.1 infection and long-term protection against the secondary Spn D39 challenge. Our study implies that an OMV vaccine delivering Spn antigens can be a new promising pneumococcal vaccine candidate.

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来源期刊
Mucosal Immunology
Mucosal Immunology 医学-免疫学
CiteScore
16.60
自引率
3.80%
发文量
100
审稿时长
12 days
期刊介绍: Mucosal Immunology, the official publication of the Society of Mucosal Immunology (SMI), serves as a forum for both basic and clinical scientists to discuss immunity and inflammation involving mucosal tissues. It covers gastrointestinal, pulmonary, nasopharyngeal, oral, ocular, and genitourinary immunology through original research articles, scholarly reviews, commentaries, editorials, and letters. The journal gives equal consideration to basic, translational, and clinical studies and also serves as a primary communication channel for the SMI governing board and its members, featuring society news, meeting announcements, policy discussions, and job/training opportunities advertisements.
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