Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, SE-171 65, Stockholm, Sweden.
Clinical Microbiology, Karolinska University Hospital, SE-171 76, Stockholm, Sweden.
Proc Natl Acad Sci U S A. 2022 Jun 7;119(23):e2122386119. doi: 10.1073/pnas.2122386119. Epub 2022 Jun 1.
Pneumococcal conjugate vaccines (PCVs) used in childhood vaccination programs have resulted in replacement of vaccine-type with nonvaccine-type pneumococci in carriage and invasive pneumococcal disease (IPD). A vaccine based on highly conserved and protective pneumococcal antigens is urgently needed. Here, we performed intranasal immunization of mice with pneumococcal membrane particles (MPs) to mimic natural nasopharyngeal immunization. MP immunization gave excellent serotype-independent protection against IPD that was antibody dependent but independent of the cytotoxin pneumolysin. Using Western blotting, immunoprecipitation, mass spectrometry, and different bacterial mutants, we identified the conserved lipoproteins MalX and PrsA as the main antigens responsible for cross-protection. Additionally, we found that omitting the variable surface protein and vaccine candidate PspA from MPs enhanced protective immune responses to the conserved proteins. Our findings suggest that MPs containing MalX and PrsA could serve as a platform for pneumococcal vaccine development targeting the elderly and immunocompromised.
肺炎球菌结合疫苗（PCV）在儿童疫苗接种计划中的应用导致了疫苗型和非疫苗型肺炎球菌在携带和侵袭性肺炎球菌病（IPD）中的更替。迫切需要一种基于高度保守和保护性肺炎球菌抗原的疫苗。在这里，我们通过鼻腔内免疫接种肺炎球菌膜颗粒（MPs）来模拟自然鼻咽免疫。MP 免疫接种可提供出色的、不受血清型影响的 IPD 保护，这种保护依赖于抗体，但不依赖于细胞毒素肺炎球菌溶血素。通过 Western blot、免疫沉淀、质谱分析和不同的细菌突变体，我们确定了保守的脂蛋白 MalX 和 PrsA 是主要的交叉保护抗原。此外，我们发现从 MPs 中去除可变表面蛋白和疫苗候选物 PspA 可增强对保守蛋白的保护性免疫反应。我们的研究结果表明，含有 MalX 和 PrsA 的 MPs 可作为针对老年人和免疫功能低下者的肺炎球菌疫苗开发的平台。
