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<p>Protein nanocages are multimeric structures that can be engineered to mimic the molecular conformation of microorganisms. Based on previous findings showing that a mucosal FlaB-tPspA fusion (flagellin fused with truncated PspA antigen of <i>Streptococcus pneumoniae</i>) vaccine-induced protective immune response against <i>S. pneumoniae</i>, we develop a ferritin nanocage vaccine displaying multivalent presentation of both antigen and adjuvant on a nanocarrier using the SpyTag/SpyCatcher strategy. The 1:1 antigen/adjuvant nanocage is further used as a mucosal vaccine, which can translocate to draining lymph nodes with higher efficiency than fusion vaccine. Moreover, intranasal immunization with the nanocage vaccine significantly enhances mucosal immune responses with more efficient B-cell memory generation and antibody maturation, as well as more balanced (Th1/Th2) immune responses with increased IFN-γ and IL-17 production, comparing with fusion vaccine. Mice immunized with the nanocage vaccine exhibited enhanced protection against lethal infection compare to the FlaB-tPspA fusion group. Our study thus demonstrates the effectiveness of an all-in-one nanocage mucosal vaccine platform, which guarantees enhanced protection with balanced immune responses.</p>

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A combined adjuvant and ferritin nanocage based mucosal vaccine against Streptococcus pneumoniae induces protective immune responses in a murine model

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月24日

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  • Tien Duc Nguyen,
  • Hoang Duy Le,
  • Giang Chau Dang,
  • Hyun Seok Jung,
  • Yoonjoo Choi,
  • Koemchhoy Khim,
  • Young Kim,
  • Shee Eun Lee,
  • Joon Haeng Rhee

摘要

Protein nanocages are multimeric structures that can be engineered to mimic the molecular conformation of microorganisms. Based on previous findings showing that a mucosal FlaB-tPspA fusion (flagellin fused with truncated PspA antigen of Streptococcus pneumoniae) vaccine-induced protective immune response against S. pneumoniae, we develop a ferritin nanocage vaccine displaying multivalent presentation of both antigen and adjuvant on a nanocarrier using the SpyTag/SpyCatcher strategy. The 1:1 antigen/adjuvant nanocage is further used as a mucosal vaccine, which can translocate to draining lymph nodes with higher efficiency than fusion vaccine. Moreover, intranasal immunization with the nanocage vaccine significantly enhances mucosal immune responses with more efficient B-cell memory generation and antibody maturation, as well as more balanced (Th1/Th2) immune responses with increased IFN-γ and IL-17 production, comparing with fusion vaccine. Mice immunized with the nanocage vaccine exhibited enhanced protection against lethal infection compare to the FlaB-tPspA fusion group. Our study thus demonstrates the effectiveness of an all-in-one nanocage mucosal vaccine platform, which guarantees enhanced protection with balanced immune responses.