Somatic Mutation and Antibody Diversity

1984 ◽  
Vol 3 (2) ◽  
pp. 139-148
Author(s):  
Michael Potter
Keyword(s):  
Somatic Mutation ◽  
Antibody Diversity

scholarly journals Development of potency, breadth and resilience to viral escape mutations in SARS-CoV-2 neutralizing antibodies

2021 ◽  
Author(s):  
Frauke Muecksch ◽  
Yiska Weisblum ◽  
Christopher O. Barnes ◽  
Fabian Schmidt ◽  
Dennis Schaefer-Babajew ◽  
...  
Keyword(s):  
Somatic Mutation ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Germinal Centers ◽  
Viral Escape ◽  
Receptor Binding Domain ◽  
Antibody Diversity ◽  
Specific Antibodies ◽  
Cognate Antigen ◽  
Pandemic Threat

SummaryAntibodies elicited in response to infection undergo somatic mutation in germinal centers that can result in higher affinity for the cognate antigen. To determine the effects of somatic mutation on the properties of SARS-CoV-2 spike receptor-binding domain (RBD)-specific antibodies, we analyzed six independent antibody lineages. As well as increased neutralization potency, antibody evolution changed pathways for acquisition of resistance and, in some cases, restricted the range of neutralization escape options. For some antibodies, maturation apparently imposed a requirement for multiple spike mutations to enable escape. For certain antibody lineages, maturation enabled neutralization of circulating SARS-CoV-2 variants of concern and heterologous sarbecoviruses. Antibody-antigen structures revealed that these properties resulted from substitutions that allowed additional variability at the interface with the RBD. These findings suggest that increasing antibody diversity through prolonged or repeated antigen exposure may improve protection against diversifying SARS-CoV-2 populations, and perhaps against other pandemic threat coronaviruses.

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