Dynamic immunodominance hierarchy of neutralizing antibody responses to evolving GII.4 noroviruses

A paradigm of RNA viruses is their ability to mutate and escape from herd immunity. Because antibody responses are a major effector for viral immunity, antigenic sites are usually under strong diversifying pressure. Here, we use norovirus as a model to study mechanisms of antigenic diversification o...

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Bibliographic Details
Main Authors: Ford-Siltz, L.A (Author), Kendra, J.A (Author), Parra, G.I (Author), Tohma, K. (Author)
Format: Article
Language:English
Published: Elsevier B.V. 2022
Subjects:
Online Access:View Fulltext in Publisher
LEADER 01917nam a2200265Ia 4500
001 10-1016-j-celrep-2022-110689
008 220425s2022 CNT 000 0 und d
020 |a 22111247 (ISSN) 
245 1 0 |a Dynamic immunodominance hierarchy of neutralizing antibody responses to evolving GII.4 noroviruses 
260 0 |b Elsevier B.V.  |c 2022 
856 |z View Fulltext in Publisher  |u https://doi.org/10.1016/j.celrep.2022.110689 
520 3 |a A paradigm of RNA viruses is their ability to mutate and escape from herd immunity. Because antibody responses are a major effector for viral immunity, antigenic sites are usually under strong diversifying pressure. Here, we use norovirus as a model to study mechanisms of antigenic diversification of non-enveloped, fast-evolving RNA viruses. We comprehensively characterize all variable antigenic sites involved in virus neutralization and find that single neutralizing monoclonal antibodies (mAbs) map to multiple antigenic sites of GII.4 norovirus. Interactions of multiple epitopes on the viral capsid surface provide a broad mAb-binding repertoire with a remarkable difference in the mAb-binding profiles and immunodominance hierarchy for two distantly related GII.4 variants. Time-ordered mutant viruses confirm a progressive change of antibody immunodominance along with point mutations during the process of norovirus evolution. Thus, in addition to point mutations, switches in immunodominance that redirect immune responses could facilitate immune escape in RNA viruses. © 2022 
650 0 4 |a antibody 
650 0 4 |a antigenic diversification 
650 0 4 |a CP: Immunology 
650 0 4 |a evolution 
650 0 4 |a humoral responses 
650 0 4 |a immunodominance 
650 0 4 |a norovirus 
650 0 4 |a RNA virus 
700 1 |a Ford-Siltz, L.A.  |e author 
700 1 |a Kendra, J.A.  |e author 
700 1 |a Parra, G.I.  |e author 
700 1 |a Tohma, K.  |e author 
773 |t Cell Reports