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Combined prime-boost immunization with systemic and mucosal pneumococcal vaccines based on Pneumococcal surface protein A to enhance protection against lethal pneumococcal infections

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Abstract

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.

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Acknowledgments

We gratefully acknowledge Editage (www.editage.cn) for the editorial support in the preparation of this manuscript.

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  1. Yue Zhang and Xiaonan Guo contributed equally to this work.

Authors and Affiliations

  1. National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, No. 2699 Qianjin Street, Changchun, 130012, People’s Republic of China

    Yue Zhang, Xiaonan Guo, Mengze Guo, Tiejun Gu, Wei Kong & Yongge Wu

  2. Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, 130012, People’s Republic of China

    Xiaorui Chen & Bo Li

  3. Thousand Oaks Biopharma(Haimen)Co., LTD, Nantong, China

    Jinfei Yu

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  1. Yue Zhang
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Zhang, Y., Guo, X., Guo, M. et al. Combined prime-boost immunization with systemic and mucosal pneumococcal vaccines based on Pneumococcal surface protein A to enhance protection against lethal pneumococcal infections. Immunol Res 67, 398–407 (2019). https://doi.org/10.1007/s12026-019-09107-6

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