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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
Authors:Wenling Wang  Renqing Li  Yao Deng  Ning Lu  Hong Chen  Xin Meng  Wen Wang  Xiuping Wang  Kexia Yan  Xiangrong Qi  Xiangmin Zhang  Wei Xin  Zhenhua Lu  Xueren Li  Tao Bian  Yingying Gao  Wenjie Tan  Li Ruan
Institution:aNational Institute for Viral Disease Control & Prevention, Chinese Center for Disease Control and Prevention (China CDC), Chang Ping District, Beijing, China;bInstitute of Immunization and Prevention, Beijing Center for Disease Control and Prevention, Dong Cheng District, Beijing, China
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.
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