title: Recombinant Adenoviruses Displaying Matrix 2 Ectodomain Epitopes on Their Fiber Proteins as Universal Influenza Vaccines.
abstract: Influenza is a zoonotic disease that poses severe threats to public health and the global economy. Reemerging influenza pandemics highlight the demand for universal influenza vaccines. We developed a novel virus platform using extracellular domain IV of the matrix 2 protein (M2e), AdC68-F3M2e, by introducing three conserved M2e epitopes into the HI loop of the chimpanzee adenovirus (AdV) fiber protein. The M2e epitopes were expressed sufficiently on the AdV virion surface without affecting fiber trimerization. Additionally, one recombinant adenovirus, AdC68-F3M2e(H1-H5-H7), induced robust M2e-specific antibody responses in BALB/c mice after two sequential vaccinations and conferred efficient protection against homologous and heterologous influenza virus (IV) challenges. We found that the use of AdV with tandem M2e epitopes in fiber is a potential strategy for influenza prevention.IMPORTANCEInfluenza epidemics and pandemics severely threaten public health. Universal influenza vaccines have increasingly attracted interest in recent years. Here, we describe a new strategy that incorporates triple M2e epitopes into the fiber protein of chimpanzee adenovirus 68. We optimized the process of inserting foreign genes into the AdC68 structural protein by one-step isothermal assembly and demonstrated that this 225-bp HI loop insertion could be well tolerated. Furthermore, two doses of adjuvant-free fiber-modified AdC68 could confer sufficient protection against homologous and heterologous influenza virus infections in mice. Our results show that AdC68-F3M2e could be pursued as a novel universal influenza vaccine.
authors.affiliation: Vaccine Research Center, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xinying
authors.initials: X
authors.lastname: Tang
authors.affiliation: Vaccine Research Center, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Vaccine Research Center, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Xia
authors.affiliation: Vaccine Research Center, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Vaccine Research Center, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Vaccine Research Center, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Yufeng
authors.initials: Y
authors.lastname: Song
authors.affiliation: Vaccine Research Center, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China.
authors.forename: Xinyi
authors.initials: X
authors.lastname: Dai
authors.affiliation: Department of Laboratory Medicine, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Min
authors.initials: M
authors.lastname: Wang
authors.affiliation: Vaccine Research Center, Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, China dmzhou@ips.ac.cn.
authors.forename: Dongming
authors.initials: D
authors.lastname: Zhou
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D002642:Chick Embryo; D003429:Cross Reactions; D000939:Epitopes / Q000276:immunology; D005260:Female; D057809:HEK293 Cells; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053127:Influenza A Virus, H9N2 Subtype / Q000276:immunology*; D007252:Influenza Vaccines / Q000276:immunology*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D008807:Mice, Inbred BALB C; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000276:immunology; D014763:Viral Matrix Proteins / Q000276:immunology*
chemical_list: D000939:Epitopes; D007252:Influenza Vaccines; D014614:Vaccines, Synthetic; D014763:Viral Matrix Proteins
keywords: HI loop; M2e; adenovirus; immune responses; universal influenza vaccine