Department of Immunology and Microbial Disease, Albany Medical College, Albany, New York, USA.
Wadsworth Center, New York State Department of Health, Albany, New York, USA.
Mucosal Immunol. 2024 Apr;17(2):169-181. doi: 10.1016/j.mucimm.2024.01.002. Epub 2024 Jan 11.
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.
肺炎链球菌（Spn）是一种常见的病原体，可在流感后引起继发性细菌感染，导致季节性和大流行流感期间严重的发病率和死亡率。因此，迫切需要开发预防严重流感后细菌性肺炎的细菌疫苗。在这里，一种改良的假结核耶尔森氏菌菌株（命名为 YptbS46）具有 Asd 质粒 pSMV92，可以合成大量的 Spn 肺炎球菌表面蛋白 A（PspA）抗原和单磷酰脂质 A 作为佐剂。重组菌株产生了含有大量 PspA 蛋白的外膜囊泡（OMV-PspA）。用 OMV-PspA 进行的肌肉内初免-加强免疫，可在接种疫苗的小鼠中诱导记忆适应性和固有免疫反应，降低病毒和细菌负担，并提供针对流感介导的继发性 Spn 感染的完全保护。此外，OMV-PspA 免疫还提供了针对继发性 Spn A66.1 感染的显著交叉保护作用，并对继发性 Spn D39 攻击提供了长期保护。我们的研究表明，递送 Spn 抗原的 OMV 疫苗可能成为一种有前途的新型肺炎球菌疫苗候选物。
