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作 者:Yihua Jiang Lingjin Sun Nan Qiao Xiang Wang Caihong Zhu Man Xing Hui Liu Ping Zhou Dongming Zhou
机构地区:[1]Department of Pathogen Biology,School of Basic Medical Sciences,Tianjin Medical University,Tianjin,300070,China [2]Shanghai Public Health Clinical Center,Fudan University,Shanghai,201508,China [3]R&D Centre,Chengdu Kanghua Biological Products Co.,Ltd,Chengdu,610000,China [4]Institut Pasteur of Shanghai,Chinese Academy of Sciences,Shanghai,200031,China
出 处:《Virologica Sinica》2024年第4期675-684,共10页中国病毒学(英文版)
基 金:supported by the National Natural Science Foundation of China(82241065,32070926)to D.Z.;the Sichuan Science and Technology Program(2023JDRC0090)to H.L.
摘 要:Norovirus(NoV)infection is a major cause of gastroenteritis worldwide.The virus poses great challenges in developing vaccines with broad immune protection due to its genetic and antigenic diversity.To date,there are no approved NoV vaccines for clinical use.Here,we aimed to develop a broad-acting quadrivalent NoV vaccine based on a chimpanzee adenovirus vector,AdC68,carrying the major capsid protein(VP1)of noroviral GI and GII genotypes.Compared to intramuscular(i.m.),intranasal(i.n.),or other prime-boost immunization regimens(i.m.t i.m.,i.m.t i.n.,i.n.t i.m.),AdC68-GI.1-GII.3(E1)-GII.4-GII.17(E3),administered via i.n.t i.n.induced higher titers of serum IgG antibodies and higher IgA antibodies in bronchoalveolar lavage fluid(BALF)and saliva against the four homologous VP1s in mice.It also significantly stimulated the production of blocking antibodies against the four genotypes.In response to re-stimulation with virus-like particles(VLP)-GI.1,VLP-GII.3,VLP-GII.4,and VLP-GII.17,the quadrivalent vaccine administered according to the i.n.t i.n.regimen effectively triggered specific cell-mediated immune responses,primarily characterized by IFN-γsecretion.Furthermore,the preparation of this novel quadrivalent NoV vaccine requires only a single recombinant adenovirus to provide broad preventive immunity against the major GI/GII epidemic strains,making it a promising vaccine candidate for further development.
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