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

TitleDevelopment of potency, breadth and resilience to viral escape mutations in SARS-CoV-2 neutralizing antibodies.
Publication TypeJournal Article
Year of Publication2021
AuthorsMuecksch 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
JournalbioRxiv
Date Published2021 Mar 08
Abstract

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.

DOI10.1101/2021.03.07.434227
Alternate JournalbioRxiv
PubMed ID33758864
PubMed Central IDPMC7987023
Grant ListR01 AI078788 / AI / NIAID NIH HHS / United States
UL1 TR001866 / TR / NCATS NIH HHS / United States
P01 AI138938 / AI / NIAID NIH HHS / United States
R37 AI064003 / AI / NIAID NIH HHS / United States
U19 AI111825 / AI / NIAID NIH HHS / United States
P41 GM103393 / GM / NIGMS NIH HHS / United States
K99 AI153465 / AI / NIAID NIH HHS / United States

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