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

Tien Duc Nguyen, Hoang Duy Le, Giang Chau Dang, Hyun Seok Jung, Yoonjoo Choi, Koemchhoy Khim, Young Kim, Shee Eun Lee () and Joon Haeng Rhee ()
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Tien Duc Nguyen: Chonnam National University
Hoang Duy Le: Chonnam National University
Giang Chau Dang: Chonnam National University
Hyun Seok Jung: Chonnam National University Medical School
Yoonjoo Choi: Chonnam National University Medical School
Koemchhoy Khim: Chonnam National University
Young Kim: Chonnam National University School of Dentistry
Shee Eun Lee: Chonnam National University
Joon Haeng Rhee: Chonnam National University

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract 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.

Date: 2025
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DOI: 10.1038/s41467-025-58115-8

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