Characterization of a Norovirus‐specific monoclonal antibody that exhibits wide spectrum binding activities

Zheng, Lijun; Wang, Wenhui; Liu, Jinjin; Chen, Xuhui; Li, Sanjing; Wang, Qiaoli; Huo, Yuqi; Qin, Chuan; Shen, Shuo; Wang, Mingchen

doi:10.1002/jmv.25001

Cited by 13 publications

(6 citation statements)

References 32 publications

(63 reference statements)

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“…However, prior to this study, GII.3 blockade antibody epitopes have not been located and verified due primarily to the lack of GII.3-specific blockade mAbs. Although two anti-GII.3 mAbs were isolated in previous studies, these mAbs had no HBGA-blocking activity, in agreement with their corresponding epitopes being mapped to the S domain, which plays no role in HBGA binding [53,54]. In the present study, we identified two GII.3-specific mAbs, 8C7 and 8D1, with potent blockade activity and mapped their corresponding epitopes to residues 385-400 and 401-420, respectively, within the P2 domain.…”

Section: Discussionsupporting

confidence: 61%

Identification of Human Norovirus GII.3 Blockade Antibody Epitopes

Wang

et al. 2021

Viruses

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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.

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Section: Discussionsupporting

confidence: 61%

Identification of Human Norovirus GII.3 Blockade Antibody Epitopes

Wang

et al. 2021

Viruses

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“…Ideally, vaccination platforms would induce broadly blocking antibodies to conserved epitopes within GI and GII strains for cross-genogroup protection, demonstrating the importance of mapping these interactions. Broadly cross-reactive epitopes common between GI and GII [54,55,56,57] or within GII strains [58,59] have been identified, primarily occurring within the distal region of the P domain, near the shell/P1 interface or within the shell domain (Table 1). Antibody access to these epitopes is likely restricted by steric hindrance in vivo, as many of these antibodies do not bind intact particles.…”

Section: Review Bodymentioning

confidence: 99%

GII.4 Human Norovirus: Surveying the Antigenic Landscape

Mallory

Lindesmith

Graham

et al. 2019

Viruses

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Human norovirus is the leading cause of viral acute onset gastroenteritis disease burden, with 685 million infections reported annually. Vulnerable populations, such as children under the age of 5 years, the immunocompromised, and the elderly show a need for inducible immunity, as symptomatic dehydration and malnutrition can be lethal. Extensive antigenic diversity between genotypes and within the GII.4 genotype present major challenges for the development of a broadly protective vaccine. Efforts have been devoted to characterizing antibody-binding interactions with dynamic human norovirus viral-like particles, which recognize distinct antigenic sites on the capsid. Neutralizing antibody functions recognizing these sites have been validated in both surrogate (ligand blockade of binding) and in vitro virus propagation systems. In this review, we focus on GII.4 capsid protein epitopes as defined by monoclonal antibody binding. As additional antibody epitopes are defined, antigenic sites emerge on the human norovirus capsid, revealing the antigenic landscape of GII.4 viruses. These data may provide a road map for the design of candidate vaccine immunogens that induce cross-protective immunity and the development of therapeutic antibodies and drugs.

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“…Previous studies have reported the isolation of broadly cross-reactive murine Abs, but none of them blocked VLPs from binding to glycans in vitro, and inhibition of replication of infectious virus using these Abs has not been determined 18 , 20 . Alpaca Abs with broad blocking activity also have been isolated 21 .…”

Section: Introductionmentioning

confidence: 99%

Broadly cross-reactive human antibodies that inhibit genogroup I and II noroviruses

et al. 2021

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The rational development of norovirus vaccine candidates requires a deep understanding of the antigenic diversity and mechanisms of neutralization of the virus. Here, we isolate and characterize a panel of broadly cross-reactive naturally occurring human monoclonal IgMs, IgAs and IgGs reactive with human norovirus (HuNoV) genogroup I or II (GI or GII). We note three binding patterns and identify monoclonal antibodies (mAbs) that neutralize at least one GI or GII HuNoV strain when using a histo-blood group antigen (HBGA) blocking assay. The HBGA blocking assay and a virus neutralization assay using human intestinal enteroids reveal that the GII-specific mAb NORO-320, mediates HBGA blocking and neutralization of multiple GII genotypes. The Fab form of NORO-320 neutralizes GII.4 infection more potently than the mAb, however, does not block HBGA binding. The crystal structure of NORO-320 Fab in complex with GII.4 P-domain shows that the antibody recognizes a highly conserved region in the P-domain distant from the HBGA binding site. Dynamic light scattering analysis of GII.4 virus-like particles with mAb NORO-320 shows severe aggregation, suggesting neutralization is by steric hindrance caused by multivalent cross-linking. Aggregation was not observed with the Fab form of NORO-320, suggesting that this clone also has additional inhibitory features.

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Characterization of a Norovirus‐specific monoclonal antibody that exhibits wide spectrum binding activities

Cited by 13 publications

References 32 publications

Identification of Human Norovirus GII.3 Blockade Antibody Epitopes

Identification of Human Norovirus GII.3 Blockade Antibody Epitopes

GII.4 Human Norovirus: Surveying the Antigenic Landscape

Broadly cross-reactive human antibodies that inhibit genogroup I and II noroviruses

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