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Human norovirus causes more than 700 million illnesses annually. Extensive genetic diversity and a paucity of information on conserved neutralizing epitopes pose major obstacles to the design of broadly protective norovirus immunogens. Here, we used high-resolution liquid chromatography-tandem mass spectrometry (LC-MS/MS)-driven proteomics to quantitatively characterize the circulating serum IgG repertoire before and after immunization with an experimental monovalent norovirus GII.4 VP1 capsid-encoding adenoviral vaccine. Two participants were specifically selected on the basis of the breadth of serum neutralization responses either across GII.4 variants (participant A) or across GII genotypes (participant B). In participant A, vaccination back-boosted highly abundant serum antibody clonotypes targeting epitopes conserved among rapidly evolving GII.4 variants spanning from a strain identified in 1987 to a strain identified in 2019. In participant B, we identified a recall response consisting of broadly neutralizing monoclonal antibodies with remarkable cross-GII ligand-binding blockade (blocking ≥ seven GII genotypes) and virus neutralization breadth. The cocrystal structure of one of these antibodies, VX22, in complex with the VP1 capsid protruding (P) domain revealed a highly conserved epitope (residues 479 to 484 and 509 to 513) within two lateral loops of the P1 subdomain. Antibody evolutionary trajectory analysis further revealed that VX22 had originally evolved from an early heterologous infection, likely by a GII.12 strain. Together, our study demonstrates that norovirus human monoclonal antibodies with broad GII.4 potency and cross-GII breadth can be boosted in serum after immunization with an adenoviral vector-based vaccine, findings that may guide the design of immunogens for broadly protective norovirus vaccines.
Pubmed ID: 40043137
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Full service sequencing core that provides both Sanger and Next Generation Sequencing services, in addition to library prep and quality check services, open access to equipment and training. Works directly with the bioinformatics core who can provide assist in any of your analysis needs to data storage solutions.
View all literature mentionsProteomics and Metabolomics services and collaborative efforts are provided at Biological Mass Spectrometry Facility. We use high resolution Orbitrap mass spectrometers with UPLC at high flow for metabolomics and nanoUPLC for proteomics work. We have Bruker Autoflex for self service MALDI. Our proteomics services are protein ID, quantitation, and modification analysis, with fractionation for deeper coverage and de novo sequencing of mAbs available. We collaborate for customized projects. We have untargeted metabolomics for quantitative or qualitative analysis of extracted metabolites using C18 column.
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