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Production, characterization and immunogenicity of P particles derived from norovirus GII.4 genotype 2004 variant

机译:诺如病毒GII.4基因型2004变体衍生的P颗粒的产生,表征和免疫原性

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Norovirus (NoV) is the main cause of nonbacterial infectious gastroenteritis. Due to the difficulty of culturing the virus, research on vaccine against NoV is focused on virus-like particles (VLPs). On the other hand, the P particles assembled from the P domains of NoV capsid protein become a promising vaccine candidate. GII.4 is the most prevalent genotype of NoV. While the immunogenicity of P particles derived from the GII.4 1996 variant has been investigated, the research on P particles of more recently prevalent variants is lacking. In this study, the P domain of the capsid protein of GII.4 genotype 2004 variant was expressed in Escherichia coli, purified and auto-assembled into P particles of 14-25 nm. Immunization with P particles induced specific serum antibodies with titers of 245,600 and 145,700 in mice and rabbits, respectively. The GII.4 NoV 2004 variant bound to type A, B and O secretor-positive saliva and immune sera blocked this binding, suggesting induction of neutralizing activity in such sera. Thus, this study demonstrated the immunogenicity of NoV P particles generated from E. coli and provided evidence supporting the development of this approach.
机译:诺如病毒(NoV)是非细菌性传染性肠胃炎的主要原因。由于难以培养病毒,因此针对NoV的疫苗的研究集中在病毒样颗粒(VLP)上。另一方面,由NoV衣壳蛋白的P结构域组装的P颗粒成为有希望的疫苗候选物。 GII.4是NoV最普遍的基因型。尽管已经研究了源自GII.4 1996变体的P颗粒的免疫原性,但仍缺乏对最近流行的变体的P颗粒的研究。在这项研究中,GII.4基因型2004变体衣壳蛋白的P结构域在大肠杆菌中表达,纯化并自动组装成14-25 nm的P颗粒。用P粒子免疫可在小鼠和兔子中分别产生245,600和145,700的特异性血清抗体。与II型,B型和O型分泌物阳性唾液结合的GII.4 NoV 2004变异体和免疫血清阻断了这种结合,表明在这种血清中诱导了中和活性。因此,这项研究证明了从大肠杆菌产生的NoV P颗粒的免疫原性,并提供了支持这种方法发展的证据。

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