tetano
Editor, Senior Moderator
J Nanobiotechnology
. 2026 Jun 26.
doi: 10.1186/s12951-026-04738-y. Online ahead of print.
Rational design of an optimized ferritin nanoparticle vaccine targeting both SARS-CoV-2 and MERS-CoV
Yaoming Liu[SUP] #[/SUP][SUP] 1 2 [/SUP], Haiyue Rao[SUP] #[/SUP][SUP] 2 [/SUP], Nana Wang[SUP] #[/SUP][SUP] 2 [/SUP], Xiaoqing Liu[SUP] 2 3 [/SUP], Tao Chen[SUP] 2 3 [/SUP], Bin Zhang[SUP] 1 2 [/SUP], Jintao Lai[SUP] 2 [/SUP], Jianyu Shan[SUP] 4 [/SUP], Shiqi Xiao[SUP] 2 [/SUP], Haojie Peng[SUP] 2 4 [/SUP], Yiqiang Zhu[SUP] 2 3 [/SUP], Taizhen Liang[SUP] 2 [/SUP], Sen Liu[SUP] 2 5 [/SUP], Meilin Hu[SUP] 2 3 [/SUP], Lixiang Xie[SUP] 2 [/SUP], Guochang Qiu[SUP] 2 4 [/SUP], Xiaobo Li[SUP] 2 [/SUP], Yaxin Li[SUP] 6 7 [/SUP], Xiancai Ma[SUP] 8 9 10 11 12 [/SUP]
Affiliations
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[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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.
Keywords: Coronaviruses; Disulfide bond; Ferritin; Nanoparticle vaccine.
. 2026 Jun 26.
doi: 10.1186/s12951-026-04738-y. Online ahead of print.
Rational design of an optimized ferritin nanoparticle vaccine targeting both SARS-CoV-2 and MERS-CoV
Yaoming Liu[SUP] #[/SUP][SUP] 1 2 [/SUP], Haiyue Rao[SUP] #[/SUP][SUP] 2 [/SUP], Nana Wang[SUP] #[/SUP][SUP] 2 [/SUP], Xiaoqing Liu[SUP] 2 3 [/SUP], Tao Chen[SUP] 2 3 [/SUP], Bin Zhang[SUP] 1 2 [/SUP], Jintao Lai[SUP] 2 [/SUP], Jianyu Shan[SUP] 4 [/SUP], Shiqi Xiao[SUP] 2 [/SUP], Haojie Peng[SUP] 2 4 [/SUP], Yiqiang Zhu[SUP] 2 3 [/SUP], Taizhen Liang[SUP] 2 [/SUP], Sen Liu[SUP] 2 5 [/SUP], Meilin Hu[SUP] 2 3 [/SUP], Lixiang Xie[SUP] 2 [/SUP], Guochang Qiu[SUP] 2 4 [/SUP], Xiaobo Li[SUP] 2 [/SUP], Yaxin Li[SUP] 6 7 [/SUP], Xiancai Ma[SUP] 8 9 10 11 12 [/SUP]
Affiliations
- PMID: 42363226
- DOI: 10.1186/s12951-026-04738-y
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[SUP]+[/SUP] and CD8[SUP]+[/SUP] 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.
Keywords: Coronaviruses; Disulfide bond; Ferritin; Nanoparticle vaccine.