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Sera Antibody Repertoire Analyses Reveal Mechanisms of Broad and Pandemic Strain Neutralizing Responses after Human Norovirus Vaccination

Immunity. 2019-06; 
Lindesmith LC, McDaniel JR, Changela A, Verardi R, Kerr SA, Costantini V, Brewer-Jensen PD, Mallory ML, Voss WN, Boutz DR, Blazeck JJ, Ippolito GC, Vinje J, Kwong PD, Georgiou G, Baric RS
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Bacterial Expression System The gene for the P-domain of HuNoV GII.4.2002 (accession number: AFJ04708) corresponding to amino acids 225-530 was synthesized by GenScript and codon optimized for E. coli expression. Get A Quote

摘要

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-G... More

关键词

antigenic seniority; epitope mapping; human monoclonal antibodies; imprinting; neutralizing antibodies; norovirus; original antigen sin; serological repertoire; vaccination; x-ray crystallography