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Leveraging MrkA Display on Self-Assembling Protein Nanoparticles for Enhanced Immune Activation
Valentina Monaci1,2, Davide Oldrini3, Fabiola Giusti4
1Magnetic Resonance Center - CERM, University of Florence, Via Luigi Sacconi 6, Sesto Fiorentino, Florence 50019, Italy.
ACS Applied Materials & Interfaces
|April 9, 2026
Summary
Protein nanoparticles displaying MrkA antigen significantly boosted immune responses against Klebsiella pneumoniae. Immunized rabbits showed 90% survival in lethal Kp challenge, highlighting potential for a new vaccine against this superbug.
Area of Science:
- Vaccinology
- Nanotechnology
- Microbiology
Background:
- Klebsiella pneumoniae is a multidrug-resistant pathogen with no existing vaccine.
- Protein nanoparticles (NPs) can enhance antigen immunogenicity via multivalent display.
- MrkA, a type 3 fimbrial subunit, is a conserved and promising vaccine target for Kp.
Purpose of the Study:
- To develop and evaluate protein nanoparticle-based vaccine candidates presenting the Kp antigen MrkA.
- To assess the immunogenicity and protective efficacy of these MrkA-NPs in animal models.
Main Methods:
- Genetically fused MrkA to four self-assembling protein NP scaffolds (H. pylori ferritin, T. maritima encapsulin, mI3, M. tuberculosis dodecin).
- Expressed, purified, and structurally confirmed MrkA-NPs.
- Evaluated immunogenicity and protective responses in animal models.
Main Results:
- All MrkA-NPs significantly enhanced MrkA-specific IgG responses and antibody titers compared to recombinant MrkA.
- Passive transfer of sera from MrkA-dodecin NP-immunized rabbits conferred 90% survival against lethal Kp challenge.
Conclusions:
- Protein NPs effectively enhance immune responses to bacterial antigens like MrkA.
- This study presents promising vaccine candidates against Kp, addressing antimicrobial resistance and global health concerns.
