Department of Biochemistry and Molecular Pharmacology; Schiffer Lab
Amino Acids, Peptides, and Proteins | Immunology of Infectious Disease | Microbiology | Virology | Virus Diseases
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.
SARS-CoV-2, antibodies, neutralization
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Copyright 2021 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
DOI of Published Version
Muecksch F, Weisblum Y, Barnes CO, Schmidt F, Schaefer-Babajew D, Wang Z, C Lorenzi JC, Flyak AI, DeLaitsch AT, Huey-Tubman KE, Hou S, Schiffer CA, Gaebler C, Da Silva J, Poston D, Finkin S, Cho A, Cipolla M, Oliveira TY, Millard KG, Ramos V, Gazumyan A, Rutkowska M, Caskey M, Nussenzweig MC, Bjorkman PJ, Hatziioannou T, Bieniasz PD. Affinity maturation of SARS-CoV-2 neutralizing antibodies confers potency, breadth, and resilience to viral escape mutations. Immunity. 2021 Aug 10;54(8):1853-1868.e7. doi: 10.1016/j.immuni.2021.07.008. Epub 2021 Jul 30. PMID: 34331873; PMCID: PMC8323339. Link to article on publisher's site
Muecksch F, Hou S, Schiffer CA, Nussenzweig MC, Bjorkman PJ, Hatziioannou T, Bieniasz PD. (2021). Affinity maturation of SARS-CoV-2 neutralizing antibodies confers potency, breadth, and resilience to viral escape mutations. COVID-19 Publications by UMMS Authors. https://doi.org/10.1016/j.immuni.2021.07.008. Retrieved from https://escholarship.umassmed.edu/covid19/291
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