Antigenic Characterization of Novel Human Norovirus GII.4 Variants San Francisco 2017 and Hong Kong 2019

Abstract

Norovirus is a major cause of acute gastroenteritis; GII.4 is the predominant strain in humans. Recently, 2 new GII.4 variants, Hong Kong 2019 and San Francisco 2017, were reported. Characterization using GII.4 monoclonal antibodies and serum demonstrated different antigenic profiles for the new variants compared with historical variants.

Keywords: GII.4 variants; Hong Kong 2019 variant; San Francisco 2017 variant; acute gastroenteritis; antigenicity; enteric infections; norovirus; viruses.

Figure 1

Monoclonal antibodies raised against 2 major GII.4 variants in a study of novel human norovirus GII.4 variants, San Francisco 2017 and Hong Kong 2019. A) Sydney 2012 mAb panel; B) Farmington Hills 2002 mAb panel. The heatmaps indicate ELISA binding strength (OD₄₀₅ values) of individual mAbs against virus-like particles from GII.4 Hong Kong 2019 and San Francisco 2017. Antibodies indicate minimal cross-reactivity between new and previously described variants. The binding sites of the mAbs were characterized in a previous study (11). mAbs, monoclonal antibodies; OD₄₀₅, optical density at 405 nm; P, protruding; S, shell.

Figure 2

HBGA blockade and binding assays in a study of novel human norovirus GII.4 variants, San Francisco 2017 and Hong Kong 2019. A,B) Line graphs indicating normalized OD₄₀₅ curves of GII.4 variants in HBGA blockade assays using mouse hyperimmune serum raised against currently circulating strains; A) Hong Kong 2019 VLPs against historical strains; B) San Francisco 2017 VLPs against historical strains. Normalized OD₄₀₅ values were calculated by using values from positive and negative (serum only) control wells. C) OD₄₀₅ curves of GII.4 variant VLPs in HGBA binding assays of Hong Kong 2019 and San Francisco 2017 VLPs and PGM III and human saliva, expressing the Lewis^a, Lewis^b, Lewis^y, H type-1, and H type-2 HBGA carbohydrates. PGM III was used as a source of HBGA carbohydrates. Human saliva was collected from a healthy adult volunteer under US Food and Drug Administration, Center for Biologics Evaluation and Research protocol no. CBER IRB 16–069B. HBGA, histo-blood group antigen; OD₄₀₅, optical density at 405 nm; PGM, porcine gastric mucin; VLP, virus-like particles.