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TitleRational design of an optimized ferritin nanoparticle vaccine targeting both SARS-CoV-2 and MERS-CoV.
Journal, issue, pagesJ Nanobiotechnology, Year 2026
Publish dateApr 3, 2026
AuthorsYaoming Liu / Haiyue Rao / Nana Wang / Xiaoqing Liu / Tao Chen / Bin Zhang / Jintao Lai / Jianyu Shan / Shiqi Xiao / Haojie Peng / Yiqiang Zhu / Taizhen Liang / Sen Liu / Meilin Hu / Lixiang Xie / Guochang Qiu / Xiaobo Li / Yaxin Li / Xiancai Ma /
PubMed AbstractBACKGROUND: Coronaviruses including SARS-CoV-2 and MERS-CoV remain threats to global health. Ferritin nanoparticle-based vaccines are promising platforms for coronaviral multivalent antigen display. ...BACKGROUND: Coronaviruses including SARS-CoV-2 and MERS-CoV remain threats to global health. Ferritin nanoparticle-based vaccines are promising platforms for coronaviral multivalent antigen display. However, their development is often constrained by limited stability and homogeneity, which hinders scale-up manufacturing and long-term storage.
RESULTS: Here, we employed artificial intelligence (AI)-guided structural modeling and optimization to introduce disulfide bonds into Helicobacter pylori ferritin (HPF). Cryo-EM at 2.2 Å confirmed the formation of inter-subunit disulfide bonds in the most promising variant HPF (I69C), resulting in a more homogeneous nanoparticle with enhanced thermal and pH stability, as well as improved solubility in physiological conditions. We utilized the ST003/SC003 molecular glue system to covalently conjugate receptor-binding domains (RBDs) of both SARS-CoV-2 and MERS-CoV, either as a mixture of individual RBD-HPF (I69C) particles or as a dimeric RBD displayed on a single HPF (I69C). Both bivalent nanoparticle vaccines elicited significantly higher titers of RBD-specific antibodies and neutralizing antibodies compared to monomeric and dimeric vaccines. Vaccination also increased frequencies of antigen-specific B cells and polyfunctional CD4 and CD8 T cells. No vaccine-related systemic abnormalities were observed. In both hACE2 and hDPP4 transgenic mice, two doses of bivalent nanoparticle vaccines provided protection against authentic SARS-CoV-2 and MERS-CoV challenges.
CONCLUSIONS: Our study demonstrated that rationally engineered HPF (I69C) produced highly stable and efficiently functionalized nanoparticle vaccines capable of eliciting potent humoral and cellular immune responses against both SARS-CoV-2 and MERS-CoV infection, thereby supporting the further development of bivalent nanoparticle vaccine platforms.
External linksJ Nanobiotechnology / PubMed:42363226
MethodsEM (single particle)
Resolution2.2 Å
Structure data

80106
EMDB Unreleased entry

25ho

EMDB-80106, PDB-25ho:
Cryo-EM structure of the Helicobacter pylori ferritin-I69C
Method: EM (single particle) / Resolution: 2.2 Å

Source
  • helicobacter pylori (bacteria)
KeywordsSTRUCTURAL PROTEIN / Protein polymer / I69C / ferritin / nanoparticle

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