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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

Engineering 2024年第1期32卷 41-56页

作者： Ram Prasad Aganja Amal Senevirathne Chandran Sivasankar John Hwa Lee Department of Veterinary Public Health College of Veterinary MedicineJeonbuk National UniversityIksan 54596Republic of Korea Department of Preventive Medicine College of Veterinary MedicineChungnam National UniversityDaejeon 34134Republic of Korea

A universal vaccine is in high demand to address the uncertainties of antigenic drift and the reduced effectiveness of current influenza *** 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 *** 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,*** protein expression was confirmed by Western blot and immunofluorescence *** 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 ***,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)***,interleukin-4(IL-4)-producing T cells were upregulated *** efficacy was demonstrated,with up to 4-fold higher production of neutralizing antibodies and a hemagglutination inhibition titer>40 against the selected viral *** 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 *** discovery revolutionizes influenza vaccine design and delivery;Salmonella-mediated COBRA-HA1 is a highly effective in vivo antigen presentation *** approach can effectively combat seasonal H1N1 influenza strains and potential pandemic outbreaks.

关键词： COBRA Influenza A Salmonella Vaccine broad spectral protection

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