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

  • Yue Zhang
  • Xiaonan Guo
  • Mengze Guo
  • Xiaorui Chen
  • Bo Li
  • Jinfei Yu
  • Tiejun Gu
  • Wei Kong
  • Yongge WuEmail author
Original Article


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.


Prime-boost immunization Pneumococcal protein vaccine Mucosal immunity PspA Streptococcus pneumoniae 



We gratefully acknowledge Editage ( for the editorial support in the preparation of this manuscript.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical standards

All mouse experiments in this paper were conducted in accordance with the Guide for the Care and Use of Laboratory Animals (National Research Council).


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Authors and Affiliations

  1. 1.National Engineering Laboratory for AIDS Vaccine, School of Life SciencesJilin UniversityChangchunPeople’s Republic of China
  2. 2.Changchun Institute of Applied Chemistry, Chinese Academy of SciencesChangchunPeople’s Republic of China
  3. 3.Thousand Oaks Biopharma(Haimen)Co., LTDNantongChina

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