title: Recombinant influenza virus carrying human adenovirus epitopes elicits protective immunity in mice.
abstract: Human adenoviruses (HAdVs) are known to cause a broad spectrum of diseases in pediatric and adult patients. As this time, there is no specific therapy for HAdV infection. This study used reverse genetics (RG) to successfully rescue a recombinant influenza virus, termed rFLU/HAdV, with the HAdV hexon protein antigenic epitope sequence inserted in the influenza non-structural (NS1) protein gene. rFLU/HAdV morphological characteristics were observed using electron microscopy. Furthermore, BALB/c mice immunized twice intranasally (i.n.) with 10(4) TCID50 or 10(5) TCID50 rFLU/HAdV showed robust humoral, mucosal, and cell-mediated immune responses in vivo. More importantly, these specific immune responses could protect against subsequent wild-type HAdV-3 (BJ809) or HAdV-7 (BJ1026) challenge, showing a significant reduction in viral load and a noticeable alleviation of histopathological changes in the challenged mouse lung in a dose-dependent manner. These findings highlighted that recombinant rFLU/HAdV warrants further investigation as a promising HAdV candidate vaccine and underscored that the immuno-protection should be confirmed in primate models.
authors.affiliation: Beijing 302 Hospital, Beijing 100039, China; Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, China.
authors.forename: Penghui
authors.initials: P
authors.lastname: Yang
authors.affiliation: Chinese PLA General Hospital, 1000853, China.
authors.forename: Tieling
authors.initials: T
authors.lastname: Li
authors.affiliation: Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Na
authors.initials: N
authors.lastname: Liu
authors.affiliation: Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, China.
authors.forename: Hongjing
authors.initials: H
authors.lastname: Gu
authors.affiliation: Chinese PLA General Hospital, 1000853, China.
authors.forename: Lina
authors.initials: L
authors.lastname: Han
authors.affiliation: Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Peirui
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Li
authors.affiliation: Beijing 302 Hospital, Beijing 100039, China.
authors.forename: Zhaohai
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Beijing 302 Hospital, Beijing 100039, China. Electronic address: zhangsg302@hotmail.com.
authors.forename: Shaogeng
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Beijing Institute of Microbiology and Epidemiology, State Key Laboratory of Pathogen and Biosecurity, Beijing 100071, China. Electronic address: xiliangw@126.com.
authors.forename: Xiliang
authors.initials: X
authors.lastname: Wang
mesh_terms: D000257:Adenoviridae Infections / Q000473:pathology / Q000517:prevention & control*; D000260:Adenoviruses, Human / Q000235:genetics / Q000276:immunology*; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D004195:Disease Models, Animal; D004337:Drug Carriers; D000939:Epitopes / Q000235:genetics / Q000276:immunology*; D005260:Female; D005822:Genetic Vectors; D006651:Histocytochemistry; D018928:Immunity, Mucosal; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008168:Lung / Q000473:pathology / Q000821:virology; D008807:Mice, Inbred BALB C; D009975:Orthomyxoviridae / Q000235:genetics*; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D059386:Reverse Genetics; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D019562:Viral Load; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000276:immunology; D014765:Viral Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D036022:Capsid Proteins; D004337:Drug Carriers; D000939:Epitopes; C085820:INS1 protein, influenza virus; D011994:Recombinant Proteins; D014614:Vaccines, Synthetic; D017361:Viral Nonstructural Proteins; D014765:Viral Vaccines; C018315:hexon capsid protein, Adenovirus
keywords: HAdV; Hexon protein epitopes; Influenza virus; Viral vector