从H1N1血凝素序列提取的沙门氏菌传递的COBRA-HA1抗原对甲型流感亚型产生广谱保护作用  

Salmonella-Delivered COBRA-HA1Antigen Derived from H1N1 Hemagglutinin Sequences Elicits Broad-Spectrum Protection Against Influenza A Subtypes

作　　者：Ram Prasad Aganja Amal Senevirathne Chandran Sivasankar John Hwa Lee 

机构地区：[1]Department of Veterinary Public Health,College of Veterinary Medicine,Jeonbuk National University,Iksan 54596,Republic of Korea [2]Department of Preventive Medicine,College of Veterinary Medicine,Chungnam National University,Daejeon 34134,Republic of Korea

出　　处：《Engineering》2024年第1期41-56,共16页工程（英文）

基　　金：Basic Science Research Program through the National Research Foundation of Korea(NRF)funded by the Ministry of Education(2019R1A6A1A03033084).

摘　　要：A universal vaccine is in high demand to address the uncertainties of antigenic drift and the reduced effectiveness of current influenza vaccines.In this study,a strategy called computationally optimized broadly reactive antigen(COBRA)was used to generate a consensus sequence of the hemagglutinin globular head portion(HA1)of influenza virus samples collected from 1918 to 2021 to trace evolutionary changes and incorporate them into the designed constructs.Constructs carrying different HA1regions were delivered into eukaryotic cells by Salmonella-mediated bactofection using a Semliki Forest virus RNA-dependent RNApolymerase(RdRp)-based eukaryotic expression system,pJHL204.Recombinant protein expression was confirmed by Western blot and immunofluorescence assays.Mice immunized with the designed constructs produced a humoral response,with a significant increase in immunoglobulin G(IgG)levels,and a cell-mediated immune response,including a 1.5-fold increase in CD4^(+) and CD8^(+)T cells.Specifically,constructs #1 and #5 increased the production of interferon-γ(IFN-γ)producing CD4^(+)and CD8^(+)T cells,skewing the response toward the T helper type 1 cell(Th1)pathway.Additionally,interleukin-4(IL-4)-producing T cells were upregulated 4-fold.Protective efficacy was demonstrated,with up to 4-fold higher production of neutralizing antibodies and a hemagglutination inhibition titer>40 against the selected viral strains.The designed constructs conferred a broadly protective immune response,resulting in a notable reduction in viral titer and minimal inflammation in the lungs of mice challenged with the influenza A/PR8/34,A/Brisbane/59/2007,A/California/07/2009,KBPV VR-92,and NCCP 43021 strains.This discovery revolutionizes influenza vaccine design and delivery;Salmonella-mediated COBRA-HA1 is a highly effective in vivo antigen presentation strategy.This approach can effectively combat seasonal H1N1 influenza strains and potential pandemic outbreaks.

关 键 词：COBRA Influenza A SALMONELLA Vaccine Broad spectral protection 

分 类 号：R73[医药卫生—肿瘤]