Identification of Human Norovirus GII.3 Blockade Antibody Epitopes

• Published in: Viruses Vol. 13; no. 10; p. 2058
• Main Authors: Yi, Yufang, Wang, Shuxia, Wang, Xiaoli, Xiong, Pei, Liu, Qingwei, Zhang, Chao, Yin, Feifei, Huang, Zhong
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 13.10.2021; MDPI
• Subjects: Amino Acid Sequence; Animals; Antibodies; Antibodies, Blocking - immunology; Antibodies, Monoclonal - immunology; Antibodies, Viral - immunology; Antigens; Binding sites; Binding Sites - genetics; Biosensors; Blood Group Antigens - genetics; Caliciviridae Infections - genetics; Capsid - immunology; Capsid protein; Capsid Proteins - genetics; Capsid Proteins - immunology; epitope; Epitopes; Epitopes - genetics; Epitopes - immunology; Gastroenteritis; Gastroenteritis - virology; Genotype; Genotypes; GII.3 genotype; histo-blood group antigens; Humans; Immunization; Mice; Monoclonal antibodies; monoclonal antibody; norovirus; Norovirus - genetics; Norovirus - immunology; Pediatrics; Phylogenetics; Plasmids; Polyethylene glycol; Protein Binding - genetics; Protein Binding - immunology; Protein Domains - genetics; Proteins; Severe acute respiratory syndrome coronavirus 2; virus-like particle; Virus-like particles; VP1 protein; United States > US; China; GII.3 genotype; histo-blood group antigens; epitope; monoclonal antibody; norovirus; virus-like particle
• ISSN: 1999-4915; 1999-4915
• DOI: 10.3390/v13102058

Human noroviruses are a common pathogen causing acute gastroenteritis worldwide. Among all norovirus genotypes, GII.3 is particularly prevalent in the pediatric population. Here we report the identification of two distinct blockade antibody epitopes on the GII.3 capsid. We generated a panel of monoclonal antibodies (mAbs) from mice immunized with virus-like particle (VLP) of a GII.3 cluster 3 strain. Two of these mAbs, namely 8C7 and 8D1, specifically bound the parental GII.3 VLP but not VLPs of GII.4, GII.17, or GI.1. In addition, 8C7 and 8D1 efficiently blocked GII.3 VLP binding with its ligand, histo-blood group antigens (HBGA). These data demonstrate that 8C7 and 8D1 are GII.3-specific blockade antibodies. By using a series of chimeric VLPs, we mapped the epitopes of 8C7 and 8D1 to residues 385-400 and 401-420 of the VP1 capsid protein, respectively. These two blockade antibody epitopes are highly conserved among GII.3 cluster 3 strains. Structural modeling shows that the 8C7 epitope partially overlaps with the HBGA binding site (HBS) while the 8D1 epitope is spatially adjacent to HBS. These findings may enhance our understanding of the immunology and evolution of GII.3 noroviruses.