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内源性 GII.4 诺如病毒样颗粒诱导的抗体缺乏对流行的 GII.17 株的交叉反应性。

The endemic GII.4 norovirus-like-particle induced-antibody lacks of cross-reactivity against the epidemic GII.17 strain.

机构信息

Division of Enteric Viral Vaccines, National Institutes for Food and Drug Control, Beijing, China.

National Vaccine and Serum Institute, Beijing, China.

出版信息

J Med Virol. 2021 Jun;93(6):3974-3979. doi: 10.1002/jmv.26474. Epub 2020 Oct 8.

Abstract

Norovirus-like particle (VLP) vaccine is promising against human norovirus infection. Unfortunately, genetic diversity of norovirus hindered the development of this vaccine. In this study, the immunogenicity of norovirus VLPs induced by the endemic GII.4 and the epidemic GII.17 genotypes, and the cross-reactivity between them as well as GI.1 and GII.3 VLPs were evaluated in mice by using serum IgG and histo-blood group antigen (HBGA) blocking antibodies as index. Results showed well immunogenicity of both GII.4 and GII.17 VLPs in mice. Serum IgG GMT (Geometric Mean Titer) were 3.63 (GII.4) and 3.88 (GII.17) respectively, and sustained to the 15th week. The HBGA blocking antibodies were 130 (GII.4) and 360 (GII.17) respectively at the end of the 4th week. Additionally, there was a dramatically statistical difference found in the cross-reactivity within genogroup (GII.3, GII.4 and GII.17) (p < .001), and also showed similar difference between genogroups (GI.1 vs. GII.3, GII.4 and GII.17) (p < .001). Summarized the pPICZa pichi pichia expression system showed a potential to be the alternative for expression of norovirus VLPs in secretion form, and the little cross-reactivity found between the endemic strain and the epidemic strain provides an evident for the consideration of selecting candidates of norovirus vaccine strains.

摘要

诺如病毒样颗粒(VLP)疫苗在预防人类诺如病毒感染方面具有广阔的应用前景。然而,诺如病毒的遗传多样性阻碍了该疫苗的开发。本研究采用血清 IgG 和组织血型抗原(HBGA)阻断抗体作为指标,评估了流行的 GII.4 和 GII.17 基因型以及 GI.1 和 GII.3 VLP 在内的地方性 GII.4 基因型 VLP 对小鼠的免疫原性及其交叉反应性。结果表明,GII.4 和 GII.17 VLP 对小鼠均具有良好的免疫原性。血清 IgG GMT(几何平均滴度)分别为 3.63(GII.4)和 3.88(GII.17),并持续到第 15 周。第 4 周末 HBGA 阻断抗体分别为 130(GII.4)和 360(GII.17)。此外,在基因群内(GII.3、GII.4 和 GII.17)观察到显著的交叉反应统计学差异(p < .001),在基因群间(GI.1 与 GII.3、GII.4 和 GII.17)也显示出类似的差异(p < .001)。综上所述,pPICZa pichi 毕赤酵母表达系统具有作为诺如病毒 VLP 分泌形式表达的替代方法的潜力,并且在地方流行株和流行株之间发现的低交叉反应性为选择诺如病毒候选疫苗株提供了依据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a66/8246737/3a7a48ebb5fb/JMV-93-3974-g002.jpg

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