Ferritin-Based HA DNA Vaccine Outperforms Conventional Designs in Inducing Protective Immunity Against Seasonal Influenza

<b>Background</b>: Influenza remains a persistent public health challenge due to antigenic drift and shift, necessitating vaccines capable of eliciting broad and durable immunity. Hemagglutinin (HA) antigen serves as the critical target for eliciting protective immune responses against i...

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Main Authors: Hongzhe Lin, Yuxuan Jiang, Yan Li, Yiwei Zhong, Mingyue Chen, Weiyu Jiang, Rong Xiang, Najing Cao, Lei Sun, Xuanyi Wang, Lu Lu, Qiao Wang, Guangyue Han, Duan Ma, Bin Wang
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Language:English
Published: MDPI AG 2025-07-01
Series:Vaccines
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Online Access:https://www.mdpi.com/2076-393X/13/7/745
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author Hongzhe Lin
Yuxuan Jiang
Yan Li
Yiwei Zhong
Mingyue Chen
Weiyu Jiang
Rong Xiang
Najing Cao
Lei Sun
Xuanyi Wang
Lu Lu
Qiao Wang
Guangyue Han
Duan Ma
Bin Wang
author_facet Hongzhe Lin
Yuxuan Jiang
Yan Li
Yiwei Zhong
Mingyue Chen
Weiyu Jiang
Rong Xiang
Najing Cao
Lei Sun
Xuanyi Wang
Lu Lu
Qiao Wang
Guangyue Han
Duan Ma
Bin Wang
author_sort Hongzhe Lin
collection DOAJ
description <b>Background</b>: Influenza remains a persistent public health challenge due to antigenic drift and shift, necessitating vaccines capable of eliciting broad and durable immunity. Hemagglutinin (HA) antigen serves as the critical target for eliciting protective immune responses against influenza. DNA vaccines offer distinct advantages over conventional platforms, including accelerated development and induction of both humoral and cellular immune responses. <b>Methods:</b> To optimize HA antigen presentation, we designed and systematically compared the immunogenicity and protective efficacy of HA antigen display strategies—bacteriophage T4 fibritin (HA-Foldon) and ferritin-based virus-like particles (HA-Ferritin)—versus monomeric HA DNA vaccines against seasonal influenza viruses. <b>Results</b>: HA-Ferritin showed superior structural stability. All vaccines induced similar HA-specific antibody levels, but HA-Ferritin elicited higher neutralizing antibodies and stronger T cell responses. Upon challenge, HA-Ferritin and HA-Foldon protected mice from weight loss and reduced lung virus loads by 3.27 and 0.76 times, respectively. Monomeric HA provided limited protection, with only 40% survival and minimal viral or pathological reduction. <b>Conclusions</b>: The HA-Ferritin DNA vaccine demonstrated enhanced immunogenicity and protection, supporting structured antigen display as a promising strategy for influenza DNA vaccine development.
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spelling doaj-art-497dc06474174e7e945405be62f5e4ff2025-08-20T03:32:16ZengMDPI AGVaccines2076-393X2025-07-0113774510.3390/vaccines13070745Ferritin-Based HA DNA Vaccine Outperforms Conventional Designs in Inducing Protective Immunity Against Seasonal InfluenzaHongzhe Lin0Yuxuan Jiang1Yan Li2Yiwei Zhong3Mingyue Chen4Weiyu Jiang5Rong Xiang6Najing Cao7Lei Sun8Xuanyi Wang9Lu Lu10Qiao Wang11Guangyue Han12Duan Ma13Bin Wang14Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education & Department of Biochemistry and Molecular Biology, Fudan University, Shanghai 200032, ChinaInstitutes of Biomedical Sciences, Fudan University, Shanghai 200032, ChinaShanghai Institute of Infectious Disease and Biosecurity, Shanghai 200032, ChinaShanghai Institute of Infectious Disease and Biosecurity, Shanghai 200032, ChinaShanghai Institute of Infectious Disease and Biosecurity, Shanghai 200032, ChinaShanghai Institute of Infectious Disease and Biosecurity, Shanghai 200032, ChinaShanghai Institute of Infectious Disease and Biosecurity, Shanghai 200032, ChinaShanghai Institute of Infectious Disease and Biosecurity, Shanghai 200032, ChinaInstitutes of Biomedical Sciences, Fudan University, Shanghai 200032, ChinaInstitutes of Biomedical Sciences, Fudan University, Shanghai 200032, ChinaShanghai Institute of Infectious Disease and Biosecurity, Shanghai 200032, ChinaShanghai Institute of Infectious Disease and Biosecurity, Shanghai 200032, ChinaHebei Provincial Center for Disease Control and Prevention, Shijiazhuang 050021, ChinaKey Laboratory of Metabolism and Molecular Medicine, Ministry of Education & Department of Biochemistry and Molecular Biology, Fudan University, Shanghai 200032, ChinaShanghai Institute of Infectious Disease and Biosecurity, Shanghai 200032, China<b>Background</b>: Influenza remains a persistent public health challenge due to antigenic drift and shift, necessitating vaccines capable of eliciting broad and durable immunity. Hemagglutinin (HA) antigen serves as the critical target for eliciting protective immune responses against influenza. DNA vaccines offer distinct advantages over conventional platforms, including accelerated development and induction of both humoral and cellular immune responses. <b>Methods:</b> To optimize HA antigen presentation, we designed and systematically compared the immunogenicity and protective efficacy of HA antigen display strategies—bacteriophage T4 fibritin (HA-Foldon) and ferritin-based virus-like particles (HA-Ferritin)—versus monomeric HA DNA vaccines against seasonal influenza viruses. <b>Results</b>: HA-Ferritin showed superior structural stability. All vaccines induced similar HA-specific antibody levels, but HA-Ferritin elicited higher neutralizing antibodies and stronger T cell responses. Upon challenge, HA-Ferritin and HA-Foldon protected mice from weight loss and reduced lung virus loads by 3.27 and 0.76 times, respectively. Monomeric HA provided limited protection, with only 40% survival and minimal viral or pathological reduction. <b>Conclusions</b>: The HA-Ferritin DNA vaccine demonstrated enhanced immunogenicity and protection, supporting structured antigen display as a promising strategy for influenza DNA vaccine development.https://www.mdpi.com/2076-393X/13/7/745DNA vaccineinfluenzahemagglutinin (HA) antigenimmunogenicityferritin-based vaccine
spellingShingle Hongzhe Lin
Yuxuan Jiang
Yan Li
Yiwei Zhong
Mingyue Chen
Weiyu Jiang
Rong Xiang
Najing Cao
Lei Sun
Xuanyi Wang
Lu Lu
Qiao Wang
Guangyue Han
Duan Ma
Bin Wang
Ferritin-Based HA DNA Vaccine Outperforms Conventional Designs in Inducing Protective Immunity Against Seasonal Influenza
Vaccines
DNA vaccine
influenza
hemagglutinin (HA) antigen
immunogenicity
ferritin-based vaccine
title Ferritin-Based HA DNA Vaccine Outperforms Conventional Designs in Inducing Protective Immunity Against Seasonal Influenza
title_full Ferritin-Based HA DNA Vaccine Outperforms Conventional Designs in Inducing Protective Immunity Against Seasonal Influenza
title_fullStr Ferritin-Based HA DNA Vaccine Outperforms Conventional Designs in Inducing Protective Immunity Against Seasonal Influenza
title_full_unstemmed Ferritin-Based HA DNA Vaccine Outperforms Conventional Designs in Inducing Protective Immunity Against Seasonal Influenza
title_short Ferritin-Based HA DNA Vaccine Outperforms Conventional Designs in Inducing Protective Immunity Against Seasonal Influenza
title_sort ferritin based ha dna vaccine outperforms conventional designs in inducing protective immunity against seasonal influenza
topic DNA vaccine
influenza
hemagglutinin (HA) antigen
immunogenicity
ferritin-based vaccine
url https://www.mdpi.com/2076-393X/13/7/745
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