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A comparison of immunogenicity of norovirus GII-4 virus-like particles and P-particles

机译:诺如病毒GII-4病毒样颗粒和P颗粒的免疫原性比较

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摘要

Norovirus (NoV) -derived virus-like particles (VLPs) resemble empty shells of the virus and NoV P-particles contain only protruding domains of the NoV capsid. Both NoV-derived subviral particles show similar functionality and antigenicity in vitro and are considered to be potential vaccine candidates against NoV gastroenteritis. BALB/c mice were immunized with baculovirus-produced GII-4 VLPs or the corresponding Escherichia coli-produced P-particles by the intramuscular or intradermal route and the NoV-specific antibody and T-cell immune responses were compared. Elevated antibody levels were induced with a single VLP immunization, whereas P-particle immunization required a boost. High avidity antibodies were raised only by VLP immunization. VLP immunization resulted in a balanced T helper type 1/type 2 immune response whereas P-particles induced a T helper type 2-biased response. Only VLP immunization primed T cells for interferon-γ production. Most importantly, cross-reactive B and T cells were induced solely by VLP immunization. In addition, VLP antiserum blocked the binding of heterotypic VLPs to human histo-blood group antigen receptor and saliva. The findings in this study are relevant for the development of NoV vaccines.
机译:诺如病毒(NoV)衍生的病毒样颗粒(VLP)类似于病毒的空壳,而NoV P颗粒仅包含NoV衣壳的突出结构域。两种NoV衍生的亚病毒颗粒在体外均显示相似的功能和抗原性,被认为是针对NoV胃肠炎的潜在疫苗候选者。通过肌内或皮内途径用杆状病毒生产的GII-4 VLP或相应的大肠杆菌生产的P颗粒免疫BALB / c小鼠,并比较NoV特异性抗体和T细胞免疫应答。一次VLP免疫可诱导抗体水平升高,而P粒子免疫则需要加强免疫。仅通过VLP免疫可产生高亲和力抗体。 VLP免疫导致平衡的1型/ 2型T辅助免疫应答,而P颗粒诱导2型的T辅助免疫应答。仅VLP免疫会引发T细胞产生干扰素-γ。最重要的是,交叉反应性B和T细胞仅通过VLP免疫诱导。此外,VLP抗血清阻断了异型VLP与人类组织血型抗原受体和唾液的结合。这项研究的发现与NoV疫苗的开发有关。

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