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

Journal Article · Sat Jun 01 00:00:00 EDT 2019 · Immunity

DOI:https://doi.org/10.1016/j.immuni.2019.05.007· OSTI ID:1526779

Lindesmith, Lisa C.; McDaniel, Jonathan R.; Changela, Anita; Verardi, Raffaello; Kerr, Scott A.; Costantini, Veronica; Brewer-Jensen, Paul D.; Mallory, Michael L.; Voss, William N.; Boutz, Daniel R.; Blazeck, John J.; Ippolito, Gregory C.; Vinje, Jan; Kwong, Peter D.; Georgiou, George; Baric, Ralph S.

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.

• Research Organization: Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
• Sponsoring Organization: USDOE Office of Science (SC), Basic Energy Sciences (BES); Vaccine Research Center; National Institute of Allergy and Infectious Diseases (NIAID); National Institutes of Health (NIH); Centers for Disease Control and Prevention (CDC); Defense Threat Reduction Agency (DTRA); Wellcome Trust
• Grant/Contract Number: W-31-109-Eng-38; R56AI106006; U19 AI109761 CETR; HDTRA1-12-C-0105; 203268/Z/16/Z
• OSTI ID: 1526779
• Alternate ID(s): OSTI ID: 1545890
• Journal Information: Immunity, Journal Name: Immunity Vol. 50 Journal Issue: 6; ISSN 1074-7613
• Publisher: Elsevier
• Country of Publication: United States
• Language: English

Related Subjects

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