期刊
IMMUNITY
卷 54, 期 8, 页码 1853-+出版社
CELL PRESS
DOI: 10.1016/j.immuni.2021.07.008
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资金
- Gordon and Betty Moore Foundation
- Beckman Foundation
- Molecular Observatory
- SLAC National Accelerator Laboratory
- US Department of Energy, Office of Science, Office of Basic Energy Sciences [DE-AC02-c76SF00515]
- SRL Structural Molecular Biology Program
- DOE Office of Biological and Environmental Research
- National Institutes of Health, National Institute of General Medical Sciences [P41GM103393]
- NIH grants [R37-AI64003, R01AI78788, P01-AI138938-S1, K99 AI153465, 2U19AI111825]
- George Mason University Fast Grant - NSF [GRFP DGE-1745301]
- Caltech Merkin Institute for Translational Research
- Hanna Gray Fellowship Program from the Howard Hughes Medical Institute
- Postdoctoral Enrichment Program from the Burroughs Wellcome Fund
- Bulgari Women & Science Fellowship in COVID-19 Research
- Robert S. Wennett PostDoctoral Fellowship
- National Center for Advancing Translational Sciences (National Institutes of Health Clinical and Translational Science Award program) [UL1 TR001866]
- Shapiro-Silverberg Fund for the Advancement of Translational Research
This study examined the development of antibodies following infection with the coronavirus, finding that evolved antibodies had increased affinity and neutralization potency, altered mutational pathways for viral resistance, and restricted neutralization escape options. These findings suggest that increasing antibody diversity through prolonged or repeated antigen exposure may improve protection against diversifying populations of the virus and other pandemic threat coronaviruses.
Antibodies elicited by infection accumulate somatic mutations in germinal centers that can increase affinity for cognate antigens. We analyzed 6 independent groups of clonally related severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) Spike receptor-binding domain (RBD)-specific antibodies from 5 individuals shortly after infection and later in convalescence to determine the impact of maturation over months. In addition to increased affinity and neutralization potency, antibody evolution changed the mutational pathways for the acquisition of viral resistance and restricted neutralization escape options. For some antibodies, maturation imposed a requirement for multiple substitutions to enable escape. For certain antibodies, affinity maturation enabled the 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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