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Human VP8*mAbs neutralize rotavirus selectively in human intestinal epithelial cells

文献类型： 外文期刊

作者： Feng, Ningguo 1 ; Hu, Liya 4 ; Ding, Siyuan 1 ; Sanyal, Mrinmoy 5 ; Zhao, Boyang 4 ; Sankaran, Banumathi 6 ; Ramani, S 1 ;

作者机构： 1.Stanford Univ, Sch Med, Dept Med, Stanford, CA 94305 USA

2.Stanford Univ, Sch Med, Dept Microbiol & Immunol, Stanford, CA 94305 USA

3.VA Palo Alto Hlth Care Syst, Palo Alto, CA USA

4.Baylor Coll Med, Dept Biochem & Mol Biol, Houston, TX 77030 USA

5.Stanford Univ, Sch Med, Dept Biochem, Stanford, CA 94305 USA

6.Lawrence Berkeley Lab, Berkeley Ctr Struct Biol Mol Biophys & Integrated, Berkeley, CA USA

7.Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA

8.Cincinnati Childrens Hosp Med Ctr, Div Infect Dis, Cincinnati, OH 45229 USA

9.Jiangsu Acad Agr Sci, Inst Vet Med, Nanjing, Jiangsu, Peoples R China

期刊名称：JOURNAL OF CLINICAL INVESTIGATION （ 影响因子：14.808； 五年影响因子：16.792 ）

ISSN： 0021-9738

年卷期： 2019 年 129 卷 9 期

页码：

收录情况： SCI

摘要： We previously generated 32 rotavirus-specific (RV-specific) recombinant monoclonal antibodies (mAbs) derived from B cells isolated from human intestinal resections. Twenty-four of these mAbs were specific for the VP8* fragment of RV VP4, and most (20 of 24) were non-neutralizing when tested in the conventional MA104 cell-based assay. We reexamined the ability of these mAbs to neutralize RVs in human intestinal epithelial cells, including ileal enteroids and HT-29 cells. Most (18 of 20) of the "non-neutralizing" VP8* mAbs efficiently neutralized human RV in HT-29 cells or enteroids. Serum RV neutralization titers in adults and infants were significantly higher in HT-29 than MA104 cells and adsorption of these sera with recombinant VP8* lowered the neutralization titers in HT-29 but not MA104 cells. VP8* mAbs also protected suckling mice from diarrhea in an in vivo challenge model. X-ray crystallographic analysis of one VP8* mAb (mAb9) in complex with human RV VP8* revealed that the mAb interaction site was distinct from the human histo-blood group antigen binding site. Since MA104 cells are the most commonly used cell line to detect anti-RV neutralization activity, these findings suggest that prior vaccine and other studies of human RV neutralization responses may have underestimated the contribution of VP8* antibodies to the overall neutralization titer.

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