Sera Antibody Repertoire Analyses Reveal Mechanisms of Broad and Pandemic Strain Neutralizing Responses after Human Norovirus Vaccination
| Autor: | Lisa C, Lindesmith, Jonathan R, McDaniel, Anita, Changela, Raffaello, Verardi, Scott A, Kerr, Veronica, Costantini, Paul D, Brewer-Jensen, Michael L, Mallory, William N, Voss, Daniel R, Boutz, John J, Blazeck, Gregory C, Ippolito, Jan, Vinje, Peter D, Kwong, George, Georgiou, Ralph S, Baric |
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| Rok vydání: | 2019 |
| Předmět: |
Models
Molecular antigenic seniority original antigen sin Protein Conformation viruses norovirus Antibodies Viral Article Cell Line Epitopes fluids and secretions Animals Humans neutralizing antibodies Amino Acid Sequence Conserved Sequence x-ray crystallography Caliciviridae Infections Vaccination virus diseases Viral Vaccines Antibodies Neutralizing Recombinant Proteins epitope mapping human monoclonal antibodies Immunoglobulin G serological repertoire imprinting Protein Binding |
| Zdroj: | Immunity |
| ISSN: | 1097-4180 |
| Popis: | Summary Rapidly evolving RNA viruses, such as the GII.4 strain of human norovirus (HuNoV), and their vaccines elicit complex serological responses associated with previous exposure. Specific correlates of protection, moreover, remain poorly understood. Here, we report the GII.4-serological antibody repertoire—pre- and post-vaccination—and select several antibody clonotypes for epitope and structural analysis. The humoral response was dominated by GII.4-specific antibodies that blocked ancestral strains or by antibodies that bound to divergent genotypes and did not block viral-entry-ligand interactions. However, one antibody, A1431, showed broad blockade toward tested GII.4 strains and neutralized the pandemic GII.P16-GII.4 Sydney strain. Structural mapping revealed conserved epitopes, which were occluded on the virion or partially exposed, allowing for broad blockade with neutralizing activity. Overall, our results provide high-resolution molecular information on humoral immune responses after HuNoV vaccination and demonstrate that infection-derived and vaccine-elicited antibodies can exhibit broad blockade and neutralization against this prevalent human pathogen. Graphical Abstract Highlights • Serum vaccine response is dominated by a small number of abundant antibody clonotypes • Vaccine-boosted antibodies predominantly target conserved norovirus epitopes • Identified cross-genogroup and strain-specific epitopes • Discovered a pandemic-genotype neutralizing antibody recognizing a conserved epitope Human norovirus (HuNoV) is a leading cause of gastroenteritis. Lindesmith et al. identify circulating serum antibodies following experimental HuNoV vaccination in humans and map them to viral epitopes. One antibody recognizes a neutralizing epitope conserved across three decades of pandemic strains and neutralizes virus in vitro, demonstrating that vaccination can elicit pandemic-strain neutralizing antibody responses in some individuals. |
| Databáze: | OpenAIRE |
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