Broad Mucosal and Systemic Immunity in Mice Induced by Intranasal Booster With a Novel Recombinant Adenoviral Based Vaccine Protects Against Divergent Influenza A Virus

Jia Li; Tangqi Wang; Xiaojuan Guo; Yujie Jiang; Liye Jin; Qiaohong Chu; Xuchang Shan; Lingfang Zhang; Ruiwen Han; Chengcheng Zhai; Donghong Wang; Yao Deng; Baoying Huang; Zhuozhuang Lu; Wenjie Tan

doi:10.1002/jmv.70326

Broad Mucosal and Systemic Immunity in Mice Induced by Intranasal Booster With a Novel Recombinant Adenoviral Based Vaccine Protects Against Divergent Influenza A Virus

J Med Virol. 2025 Apr;97(4):e70326. doi: 10.1002/jmv.70326.

Authors

Jia Li¹, Tangqi Wang^{1

2}, Xiaojuan Guo², Yujie Jiang¹, Liye Jin³, Qiaohong Chu², Xuchang Shan³, Lingfang Zhang⁴, Ruiwen Han^{1

2}, Chengcheng Zhai², Donghong Wang², Yao Deng², Baoying Huang², Zhuozhuang Lu², Wenjie Tan^{1

2}

Affiliations

¹ Zhejiang Provincial Key Laboratory of Medical Genetics, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou, China.
² National Key Laboratory of Intelligent Tracking and Forecasting for Infectious Diseases, Key Laboratory of Biosafety, National Health Commissions, National Institute for Viral Disease Control and Prevention, China CDC, Beijing, China.
³ School of Public Health, Xinxiang Medical University, Xinxiang, China.
⁴ School of Basic Medical Sciences, Inner Mongolia Medical University, Hohhot, China.

PMID: 40145257
DOI: 10.1002/jmv.70326

Abstract

The development of broad-spectrum universal influenza vaccines and optimization of vaccination strategies to address the threats posed by pandemics and emerging influenza viruses are critical for public health. In this study, an adenovirus type 5 vector-based influenza vaccine carrying the hemagglutinin (HA) stem of H1, HA stem of H3, and neuraminidase (NA) of N1 from the influenza virus was constructed. Immune responses were evaluated in mice using various vaccination strategies: prime-only (intramuscular [IM] or intranasal [IN]) and prime-boost (IM + IN). Compared with the prime-only strategy, the prime-boost strategy significantly enhanced the systemic immune response, inducing higher levels of antigen-specific IgG, mucosal IgA, and T cell immunity in the spleen and lungs. Furthermore, the IN boosting strategy provided complete protection in mice challenged with the H1N1-PR8, rgH3N2-X31, and rgH5N1-Vietnam viruses, significantly reducing viral loads in the lungs and alleviating lung tissue pathologies. In conclusion, this study elucidates potential avenues for the development and application of universal influenza vaccines using customized mucosal boosting strategies.

Keywords: adenovirus vector‐based influenza vaccine; intranasal booster; mucosal immunity; systemic immunity; universal influenza vaccine.

MeSH terms

Adenoviridae / genetics
Administration, Intranasal
Animals
Antibodies, Viral / analysis
Antibodies, Viral / blood
Female
Genetic Vectors
Hemagglutinin Glycoproteins, Influenza Virus / genetics
Hemagglutinin Glycoproteins, Influenza Virus / immunology
Immunity, Mucosal*
Immunization, Secondary* / methods
Immunoglobulin A / analysis
Immunoglobulin G / analysis
Influenza A virus* / genetics
Influenza A virus* / immunology
Influenza Vaccines* / administration & dosage
Influenza Vaccines* / genetics
Influenza Vaccines* / immunology
Lung / immunology
Lung / pathology
Lung / virology
Mice
Mice, Inbred BALB C
Orthomyxoviridae Infections* / immunology
Orthomyxoviridae Infections* / prevention & control
Orthomyxoviridae Infections* / virology
Spleen / immunology
T-Lymphocytes / immunology
Vaccines, Synthetic / administration & dosage
Vaccines, Synthetic / genetics
Vaccines, Synthetic / immunology
Viral Load

Substances

Influenza Vaccines
Antibodies, Viral
Vaccines, Synthetic
Immunoglobulin A
Immunoglobulin G
Hemagglutinin Glycoproteins, Influenza Virus

Grants and funding

This study was supported by grants from the National Key Research and Development Program of China [grant number 2022YFC2304100] and the National Natural Science Foundation of China (82041041).