title: Protective Efficacy of the Conserved NP, PB1, and M1 Proteins as Immunogens in DNA- and Vaccinia Virus-Based Universal Influenza A Virus Vaccines in Mice.
abstract: The conventional hemagglutinin (HA)- and neuraminidase (NA)-based influenza vaccines need to be updated most years and are ineffective if the glycoprotein HA of the vaccine strains is a mismatch with that of the epidemic strain. Universal vaccines targeting conserved viral components might provide cross-protection and thus complement and improve conventional vaccines. In this study, we generated DNA plasmids and recombinant vaccinia viruses expressing the conserved proteins nucleoprotein (NP), polymerase basic 1 (PB1), and matrix 1 (M1) from influenza virus strain A/Beijing/30/95 (H3N2). BALB/c mice were immunized intramuscularly with a single vaccine based on NP, PB1, or M1 alone or a combination vaccine based on all three antigens and were then challenged with lethal doses of the heterologous influenza virus strain A/PR/8/34 (H1N1). Vaccines based on NP, PB1, and M1 provided complete or partial protection against challenge with 1.7 50% lethal dose (LD50) of PR8 in mice. Of the three antigens, NP-based vaccines induced protection against 5 LD50 and 10 LD50 and thus exhibited the greatest protective effect. Universal influenza vaccines based on the combination of NP, PB1, and M1 induced a strong immune response and thus might be an alternative approach to addressing future influenza virus pandemics.
authors.affiliation: National Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control and Prevention (China CDC), Chang Ping District, Beijing, China.
authors.forename: Wenling
authors.initials: W
authors.lastname: Wang
authors.affiliation: National Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control and Prevention (China CDC), Chang Ping District, Beijing, China Institute of Immunization and Prevention, Beijing Center for Disease Control and Prevention, Dong Cheng District, Beijing, China.
authors.forename: Renqing
authors.initials: R
authors.lastname: Li
authors.affiliation: National Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control and Prevention (China CDC), Chang Ping District, Beijing, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Deng
authors.affiliation: National Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control and Prevention (China CDC), Chang Ping District, Beijing, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Lu
authors.affiliation: National Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control and Prevention (China CDC), Chang Ping District, Beijing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: National Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control and Prevention (China CDC), Chang Ping District, Beijing, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Meng
authors.affiliation: National Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control and Prevention (China CDC), Chang Ping District, Beijing, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Wang
authors.affiliation: National Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control and Prevention (China CDC), Chang Ping District, Beijing, China.
authors.forename: Xiuping
authors.initials: X
authors.lastname: Wang
authors.affiliation: National Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control and Prevention (China CDC), Chang Ping District, Beijing, China.
authors.forename: Kexia
authors.initials: K
authors.lastname: Yan
authors.affiliation: National Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control and Prevention (China CDC), Chang Ping District, Beijing, China.
authors.forename: Xiangrong
authors.initials: X
authors.lastname: Qi
authors.affiliation: National Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control and Prevention (China CDC), Chang Ping District, Beijing, China.
authors.forename: Xiangmin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: National Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control and Prevention (China CDC), Chang Ping District, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Xin
authors.affiliation: National Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control and Prevention (China CDC), Chang Ping District, Beijing, China.
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Lu
authors.affiliation: National Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control and Prevention (China CDC), Chang Ping District, Beijing, China.
authors.forename: Xueren
authors.initials: X
authors.lastname: Li
authors.affiliation: National Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control and Prevention (China CDC), Chang Ping District, Beijing, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Bian
authors.affiliation: National Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control and Prevention (China CDC), Chang Ping District, Beijing, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Gao
authors.affiliation: National Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control and Prevention (China CDC), Chang Ping District, Beijing, China.
authors.forename: Wenjie
authors.initials: W
authors.lastname: Tan
authors.affiliation: National Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control and Prevention (China CDC), Chang Ping District, Beijing, China ruanlicdc@163.com.
authors.forename: Li
authors.initials: L
authors.lastname: Ruan
mesh_terms: D000818:Animals; D056738:Cross Protection; D004195:Disease Models, Animal; D004337:Drug Carriers; D005260:Female; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D007273:Injections, Intramuscular; D008807:Mice, Inbred BALB C; D019590:Nucleocapsid Proteins; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control; D016601:RNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D016019:Survival Analysis; D016896:Treatment Outcome; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D014614:Vaccines, Synthetic / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology; D014616:Vaccinia virus / Q000235:genetics*; D014758:Viral Core Proteins / Q000235:genetics / Q000276:immunology*; D014763:Viral Matrix Proteins / Q000235:genetics / Q000276:immunology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology*
chemical_list: D004337:Drug Carriers; D007252:Influenza Vaccines; C488936:M1 protein, Influenza A virus; C048842:NP protein, Influenza A virus; D019590:Nucleocapsid Proteins; D016601:RNA-Binding Proteins; D019444:Vaccines, DNA; D014614:Vaccines, Synthetic; D014758:Viral Core Proteins; D014763:Viral Matrix Proteins; D014764:Viral Proteins; C077346:influenza virus polymerase basic protein 1
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