Characterization of Blockade Antibody Responses in GII.2.1976 Snow Mountain Virus-Infected Subjects

Swanstrom, Jesica; Lindesmith, Lisa C.; Donaldson, Eric F.; Yount, Boyd; Baric, Ralph S.

doi:10.1128/jvi.02793-13

Cited by 34 publications

(37 citation statements)

References 49 publications

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“…All of the VLPs used in this study bind to ligands found in porcine gastric mucin (PGM) type III, with the exception of GII.2. Although bioinformatics analyses do not suggest why, GII.2 does not bind to any identified HBGA sources except human type A and B saliva [ 43 ]; therefore, blockade assays were not performed for this VLP.…”

Section: Methodsmentioning

confidence: 99%

Broad Blockade Antibody Responses in Human Volunteers after Immunization with a Multivalent Norovirus VLP Candidate Vaccine: Immunological Analyses from a Phase I Clinical Trial

et al. 2015

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BackgroundHuman noroviruses (NoVs) are the primary cause of acute gastroenteritis and are characterized by antigenic variation between genogroups and genotypes and antigenic drift of strains within the predominant GII.4 genotype. In the context of this diversity, an effective NoV vaccine must elicit broadly protective immunity. We used an antibody (Ab) binding blockade assay to measure the potential cross-strain protection provided by a multivalent NoV virus-like particle (VLP) candidate vaccine in human volunteers.Methods and FindingsSera from ten human volunteers immunized with a multivalent NoV VLP vaccine (genotypes GI.1/GII.4) were analyzed for IgG and Ab blockade of VLP interaction with carbohydrate ligand, a potential correlate of protective immunity to NoV infection and illness. Immunization resulted in rapid rises in IgG and blockade Ab titers against both vaccine components and additional VLPs representing diverse strains and genotypes not represented in the vaccine. Importantly, vaccination induced blockade Ab to two novel GII.4 strains not in circulation at the time of vaccination or sample collection. GII.4 cross-reactive blockade Ab titers were more potent than responses against non-GII.4 VLPs, suggesting that previous exposure history to this dominant circulating genotype may impact the vaccine Ab response. Further, antigenic cartography indicated that vaccination preferentially activated preexisting Ab responses to epitopes associated with GII.4.1997. Study interpretations may be limited by the relevance of the surrogate neutralization assay and the number of immunized participants evaluated.ConclusionsVaccination with a multivalent NoV VLP vaccine induces a broadly blocking Ab response to multiple epitopes within vaccine and non-vaccine NoV strains and to novel antigenic variants not yet circulating at the time of vaccination. These data reveal new information about complex NoV immune responses to both natural exposure and to vaccination, and support the potential feasibility of an efficacious multivalent NoV VLP vaccine for future use in human populations.Trial RegistrationClinicalTrials.gov NCT01168401

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Section: Methodsmentioning

confidence: 99%

Broad Blockade Antibody Responses in Human Volunteers after Immunization with a Multivalent Norovirus VLP Candidate Vaccine: Immunological Analyses from a Phase I Clinical Trial

et al. 2015

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“…Consistent with this, human sera from GI.1-challenged volunteers contained blockade responses effective against multiple genogroup I genotypes (Lindesmith et al, 2010). The GII.2 cluster also acquires limited antigenic changes in its VP1 protein (Swanstrom et al, 2014). Interestingly, GII.3 viruses which are predominantly associated with pediatric infections evolve as rapidly as GII.4 viruses at the genomic level but revert back to previously used residues at the protein level (Boon et al, 2011).…”

Section: Noroviruses Are Under Humoral Selectionmentioning

confidence: 99%

Advances in Norovirus Biology

Karst

Wobus

Goodfellow

et al. 2014

Cell Host & Microbe

189

208

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Human noroviruses are a major cause of epidemic and sporadic gastroenteritis worldwide, and can chronically infect immunocompromised patients. Efforts to develop effective vaccines and antivirals have been hindered by the uncultivable nature and extreme genetic diversity of human noroviruses. Although they remain a particularly challenging pathogen to study, recent advances in norovirus animal models and in vitro cultivation systems have led to an increased understanding of norovirus molecular biology and replication, pathogenesis, cell tropism, and innate and adaptive immunity. Furthermore, clinical trials of vaccines consisting of nonreplicating virus-like particles have shown promise. In this review, we summarize these recent advances and discuss controversies in the field, which is rapidly progressing towards generation of antiviral agents and increasingly effective vaccines.

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“…The impact of NoV diversity on the breadth and duration of protective immunity remains poorly understood. Some previous experimental NoV challenge studies and epidemiologic studies suggested that NoVs elicit antibodies with intragenogroup cross-reactivity (15)(16)(17)(18)(19)(20)(21)(22), while other studies reported evidence for intergenogroup cross-reactive serum antibody (23)(24)(25)(26)(27)(28).…”

mentioning

confidence: 98%

Experimental Human Infection with Norwalk Virus Elicits a Surrogate Neutralizing Antibody Response with Cross-Genogroup Activity

Czakó

Atmar

Opekun

et al. 2014

Clin. Vaccine Immunol.

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The human noroviruses (NoVs) are genetically diverse, rapidly evolving RNA viruses and are the major cause of epidemic gastroenteritis of humans. Serum antibodies that block the interaction of NoVs and NoV viruslike particles (VLPs) with host attachment factors are considered surrogate neutralizing antibodies in the absence of cell culture and small-animal replication models for the human NoVs. A serological assay for NoV-blocking antibodies was used to assess the breadth of the heterotypic antibody response in the context of an experimental challenge study with a human NoV. Heterotypic histo-blood group antigen (HBGA)-blocking activity against GI.4, GI.7, and GII.4 NoVs increased significantly in the serum of individuals (n = 18) infected with Norwalk virus (GI.1). Although the fold increases and peak titers of heterotypic antibody were more modest than titers of antibody reactive with the challenge antigen, Norwalk virus infection elicited a serological rise even against the novel Sydney variant of GII.4 NoVs. These observations indicate that the development of a broadly cross-protective NoV vaccine containing a limited number of genotypes may be possible.

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Characterization of Blockade Antibody Responses in GII.2.1976 Snow Mountain Virus-Infected Subjects

Cited by 34 publications

References 49 publications

Broad Blockade Antibody Responses in Human Volunteers after Immunization with a Multivalent Norovirus VLP Candidate Vaccine: Immunological Analyses from a Phase I Clinical Trial

Broad Blockade Antibody Responses in Human Volunteers after Immunization with a Multivalent Norovirus VLP Candidate Vaccine: Immunological Analyses from a Phase I Clinical Trial

Advances in Norovirus Biology

Experimental Human Infection with Norwalk Virus Elicits a Surrogate Neutralizing Antibody Response with Cross-Genogroup Activity

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