Department of Molecular Genetics and Infection Biology, Interfaculty Institute of Genetics and Functional Genomics, Center for Functional Genomics of Microbes, University of Greifswald, Greifswald, Germany.
Division of Bioanalytical Chemistry, Research Center Borstel - Leibniz Lung Center, Borstel, Germany.
Front Immunol. 2024 Apr 22;15:1392316. doi: 10.3389/fimmu.2024.1392316. eCollection 2024.
remains a significant global threat, with existing vaccines having important limitations such as restricted serotype coverage and high manufacturing costs. Pneumococcal lipoproteins are emerging as promising vaccine candidates due to their surface exposure and conservation across various serotypes. While prior studies have explored their potential in mice, data in a human context and insights into the impact of the lipid moiety remain limited. In the present study, we examined the immunogenicity of two pneumococcal lipoproteins, DacB and MetQ, both in lipidated and non-lipidated versions, by stimulation of primary human immune cells. Immune responses were assessed by the expression of common surface markers for activation and maturation as well as cytokines released into the supernatant. Our findings indicate that in the case of MetQ lipidation was crucial for activation of human antigen-presenting cells such as dendritic cells and macrophages, while non-lipidated DacB demonstrated an intrinsic potential to induce an innate immune response. Nevertheless, immune responses to both proteins were enhanced by lipidation. Interestingly, following stimulation of dendritic cells with DacB, LipDacB and LipMetQ, cytokine levels of IL-6 and IL-23 were significantly increased, which are implicated in triggering potentially important Th17 cell responses. Furthermore, LipDacB and LipMetQ were able to induce proliferation of CD4+ T cells indicating their potential to induce an adaptive immune response. These findings contribute valuable insights into the immunogenic properties of pneumococcal lipoproteins, emphasizing their potential role in vaccine development against pneumococcal infections.
肺炎球菌仍然是一个重大的全球威胁，现有的疫苗存在重要的局限性，如血清型覆盖范围有限和制造成本高。肺炎球菌脂蛋白因其在不同血清型中的表面暴露和保守性而成为有前途的疫苗候选物。虽然先前的研究已经在小鼠中探索了它们的潜力，但在人类背景下的数据和对脂质部分影响的了解仍然有限。在本研究中，我们通过刺激原代人免疫细胞，研究了两种肺炎球菌脂蛋白 DacB 和 MetQ 的免疫原性，包括脂化和非脂化版本。通过常见的表面标记物的表达来评估免疫反应的激活和成熟程度，以及细胞因子释放到上清液中。我们的研究结果表明，在 MetQ 的情况下，脂化对于激活树突状细胞和巨噬细胞等人类抗原呈递细胞至关重要，而非脂化的 DacB 表现出内在的诱导先天免疫反应的潜力。然而，脂化增强了对这两种蛋白质的免疫反应。有趣的是，在用 DacB、LipDacB 和 LipMetQ 刺激树突状细胞后，IL-6 和 IL-23 的细胞因子水平显著增加，这与触发潜在重要的 Th17 细胞反应有关。此外，LipDacB 和 LipMetQ 能够诱导 CD4+T 细胞的增殖，表明它们有潜力诱导适应性免疫反应。这些发现为肺炎球菌脂蛋白的免疫原性提供了有价值的见解，强调了它们在开发针对肺炎球菌感染的疫苗方面的潜在作用。
