Limited protective effects of commercially available vaccines necessitate the development of novel pneumococcal vaccines. We recently reported a pneumococcal systemic vaccine containing two proteins, Pneumococcal surface protein A (PspA of family 1 and 2) and a bacterium-like particle-based pneumococcal mucosal vaccine containing PspA2 and PspA4 fragments, both eliciting broad protective immune responses. We had previously reported that subcutaneous (s.c.+s.c.+s.c.) immunization with the systemic vaccine induced more pronounced humoral serum IgG responses, while intranasal (i.n.+i.n.+i.n.) immunization with the mucosal vaccine elicited a more pronounced mucosal secretory IgA (sIgA) response. We hypothesized that a combinatorial administration of the two vaccines might elicit more pronounced and broader protective immune responses. Therefore, this study aimed to determine the efficacy of combinatorial prime-boost immunization using both systemic and mucosal vaccines for a pneumococcal infection. Combinatorial prime-boost immunization (s.c.+i.n. and i.n.+s.c.) induced not only IgG, but also mucosal sIgA production at high levels. Systemic priming and mucosal boosting immunization (s.c.+i.n.) provided markedly better protection than homologous prime-boost immunization (s.c.+s.c.+s.c. and i.n.+i.n.+i.n.). Moreover, it induced more robust Th1 and Th17 cell-mediated immune responses than mucosal priming and systemic boosting immunization (i.n.+s.c.). These results indicate that combinatorial prime-boost immunization potentially induces a robust systemic and mucosal immune response, making it an optimal alternative for maximum protection against lethal pneumococcal infections.

中文翻译：

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将初免-加强免疫与基于肺炎球菌表面蛋白A的全身和粘膜肺炎球菌疫苗联合使用，以增强针对致命性肺炎球菌感染的保护。

市售疫苗的有限的保护作用需要开发新型的肺炎球菌疫苗。我们最近报道了一种肺炎球菌全身疫苗，其中包含两种蛋白：肺炎球菌表面蛋白A（家族1和2的PspA）和一种含有PspA2和PspA4片段的细菌样颗粒状肺炎球菌粘膜疫苗，均引起广泛的保护性免疫应答。我们之前曾报道过，全身性疫苗皮下（sc + sc + sc）免疫诱导了更明显的体液血清IgG反应，而粘膜疫苗的鼻内（in + in + in）免疫引起了更明显的粘膜分泌性IgA（sIgA）响应。我们假设两种疫苗的组合给药可能引起更明显和更广泛的保护性免疫应答。因此，这项研究的目的是确定使用全身和粘膜疫苗进行肺炎球菌感染的组合初免-加强免疫的功效。组合初免-加强免疫（sc + in和in + sc）不仅诱导IgG，而且还诱导高水平的粘膜sIgA产生。系统性初免和粘膜加强免疫（sc + in）提供了比同源初免-加强免疫（sc + sc + sc和in + in + in）更好的保护。此外，它比粘膜引发和全身加强免疫（in + sc）诱导更强的Th1和Th17细胞介导的免疫反应。这些结果表明，组合的初免-加强免疫可能诱导强大的全身和粘膜免疫反应，使其成为针对致命性肺炎球菌感染提供最大保护的最佳选择。