Lymph Node Follicle-Targeting STING Agonist Nanoshells Enable Single-Shot M2e Vaccination for Broad and Durable Influenza Protection

Hsiao Han Tsai, Ping Han Huang, Leon C.W. Lin, Bing Yu Yao, Wan Ting Liao, Chen Hsueh Pai, Yu Han Liu, Hui Wen Chen, Che Ming J. Hu

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

The highly conserved matrix protein 2 ectodomain (M2e) of influenza viruses presents a compelling vaccine antigen candidate for stemming the pandemic threat of the mutation-prone pathogen, yet the low immunogenicity of the diminutive M2e peptide renders vaccine development challenging. A highly potent M2e nanoshell vaccine that confers broad and durable influenza protectivity under a single vaccination is shown. Prepared via asymmetric ionic stabilization for nanoscopic curvature formation, polymeric nanoshells co-encapsulating high densities of M2e peptides and stimulator of interferon genes (STING) agonists are prepared. Robust and long-lasting protectivity against heterotypic influenza viruses is achieved with a single administration of the M2e nanoshells in mice. Mechanistically, molecular adjuvancy by the STING agonist and nanoshell-mediated prolongation of M2e antigen exposure in the lymph node follicles synergistically contribute to the heightened anti-M2e humoral responses. STING agonist-triggered T cell helper functions and extended residence of M2e peptides in the follicular dendritic cell network provide a favorable microenvironment that induces Th1-biased antibody production against the diminutive antigen. These findings highlight a versatile nanoparticulate design that leverages innate immune pathways for enhancing the immunogenicity of weak immunogens. The single-shot nanovaccine further provides a translationally viable platform for pandemic preparedness.

Original languageEnglish (US)
Article number2206521
JournalAdvanced Science
Volume10
Issue number17
DOIs
StatePublished - Jun 13 2023
Externally publishedYes

Keywords

  • follicular dendritic cells
  • germinal center
  • lymph node follicle targeting
  • matrix protein 2 ectodomain antigen
  • nanoshell
  • stimulator of interferon genes agonist
  • universal influenza vaccine

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • General Chemical Engineering
  • General Materials Science
  • Biochemistry, Genetics and Molecular Biology (miscellaneous)
  • General Engineering
  • General Physics and Astronomy

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