Linear epitopes on the capsid protein of norovirus commonly elicit high antibody response among past-infected individuals

• Published in: Virology journal Vol. 20; no. 1; p. 115
• Main Authors: Deng, Yilin, He, Taojun, Li, Bin, Yuan, Hanmei, Zhang, Fang, Wu, Hui, Ning, Jie, Zhang, Yanping, Zhai, Aixia, Wu, Chao
• Format: Journal Article
• Language: English
• Published: London BioMed Central 06.06.2023; BioMed Central Ltd; BMC
• Subjects: Amino acids; Analysis; antibody formation; Antibody response; Antigenic determinants; Antigens; antiserum; B-lymphocytes; Biomedical and Life Sciences; Biomedicine; blood serum; Broadly protective anti-viral vaccines; capsid; Capsid protein; Causes of; Chemical properties; Chromatography; coat proteins; Development and progression; Enzyme-linked immunosorbent assay; Epitopes; Gastroenteritis; Health aspects; humans; Identification and classification; IgG; Immune response; Immunoglobulin G; Infection; Infections; insects; ion exchange chromatography; Lymphocytes B; Monoclonal antibodies; Norovirus; people; Peptides; Prevention; Proteins; Sucrose; Vaccines; Viral infections; Viral proteins; Virology; Virus diseases; Virus-like particles; VP1; VP1 protein; VP2; China; United States > US; IgG; VP2; Norovirus; Epitopes; VP1
• ISSN: 1743-422X; 1743-422X
• DOI: 10.1186/s12985-023-02087-y

Background Human norovirus (HuNoV) is the leading cause of acute nonbacterial gastroenteritis globally, and its infection is usually self-limited, so most people become past Norovirus (NoV)-infected individuals. It is known that some antibody responses may play a critical role in preventing viral infection and alleviating disease; however, the characteristics and functions of particular antibody responses in persons with previous infections are not fully understood. Capsid proteins, including VP1 and VP2, are crucial antigenic components of NoV and may regulate antibody immune responses, while epitope-specific antibody responses to capsid proteins have not been comprehensively characterized. Methods We prepared purified VP1 and VP2 proteins by ion exchange chromatography and measured serum antigen-specific IgG levels in 398 individuals by ELISA. Overlapping 18-mer peptides covering the full length of VP1 and VP2 were synthesized, and then we identified linear antigenic epitopes from 20 subjects with strong IgG positivity. Subsequently, specific antibody responses to these epitopes were validated in 185 past infected individuals, and the conservation of epitopes was analyzed. Finally, we obtained epitope-specific antiserum by immunizing mice and expressed virus-like particles (VLPs) in an insect expression system for a blockade antibody assay to evaluate the receptor-blocking ability of epitope-specific antibodies. Results The IgG responses of VP1 were significantly stronger than those of VP2, both of which had high positive rates of over 80%. The overall positive rate of VP1-IgG and/or VP2-IgG was approximately 94%, which may be past NoV-infected individuals. Four linear antigenic B-cell epitopes of capsid proteins were identified, namely, VP1 199–216 , VP1 469–492 , VP2 97–120, and VP2 241–264 , all of which were conserved. The IgG response rates of the above epitopes in past NoV-infected individuals were 38.92%, 22.16%, 8.11% and 28.11%, respectively. In addition, VP1 199–216 - and VP1 469–492 -specific antibodies can partially block the binding of VLPs to the receptor histo-blood group antigen (HBGA). Conclusion This is the first study to describe specific antibody responses of VP2 and to identify its B-cell epitopes. Our findings offer data for a more thorough understanding of norovirus capsid protein-specific IgG responses and could provide useful information for designing and developing vaccines.