Department of Biochemistry and Molecular Pharmacology; Schiffer Lab
Amino Acids, Peptides, and Proteins | Immunology of Infectious Disease | Microbiology | Virology | Virus Diseases
Antibodies 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.
microbiology, SARS-CoV-2, Antibodies, Neutralization
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DOI of Published Version
Muecksch F, Weisblum Y, Barnes CO, Schmidt F, Schaefer-Babajew D, Lorenzi JCC, Flyak AI, DeLaitsch AT, Huey-Tubman KE, Hou S, Schiffer CA, Gaebler C, Wang Z, 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. Development of potency, breadth and resilience to viral escape mutations in SARS-CoV-2 neutralizing antibodies. bioRxiv [Preprint]. 2021 Mar 8:2021.03.07.434227. doi: 10.1101/2021.03.07.434227. PMID: 33758864; PMCID: PMC7987023. Link to preprint on bioRxiv.
Now published in Cell, doi:10.1016/j.immuni.2021.07.008
Muecksch F, Hou S, Schiffer CA, Nussenzweig M, Bjorkman PJ, Hatziioannou T, Bieniasz P. (2021). Development of potency, breadth and resilience to viral escape mutations in SARS-CoV-2 neutralizing antibodies [preprint]. University of Massachusetts Medical School Faculty Publications. https://doi.org/10.1101/2021.03.07.434227. Retrieved from https://escholarship.umassmed.edu/faculty_pubs/1925
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