Vaccination of SARS-CoV-2-infected individuals expands a broad range of clonally diverse affinity-matured B cell lineages

Autor: Mark Chernyshev, Mrunal Sakharkar, Ruth Connor, Haley Dugan, Daniel Sheward, C. Garrett Rappazzo, Aron Stålmarck, Mattias Forsell, Peter Wright, Martin Corcoran, Ben Murrell, Laura Walker, Gunilla Karlsson Hedestam
Rok vydání: 2022
DOI: 10.21203/rs.3.rs-2231608/v1
Popis: Vaccination of SARS-CoV-2 convalescent individuals generates broad and potent antibody responses. Here, we isolated 459 spike-specific monoclonal antibodies (mAbs) from two individuals who were infected with an early ancestral strain of SARS-CoV-2 and later boosted with mRNA-1273. We characterized mAb genetic features by sequence assignments to the donors’ personal immunoglobulin genotypes and assessed antibody neutralizing activities against ancestral SARS-CoV-2, Beta, Delta, and Omicron variants. The mAbs used a broad range of immunoglobulin heavy chain (IGH) V genes in the response to all sub-determinants of the spike examined, with similar characteristics observed in both donors. IGH repertoire sequencing and B cell lineage tracing at longitudinal time points revealed extensive evolution of SARS-CoV-2 spike-binding antibodies from acute infection until vaccination five months later. These results demonstrate that highly polyclonal repertoires of affinity-matured memory B cells were efficiently recalled by vaccination, providing a basis for the potent antibody responses observed in convalescent persons following vaccination.
Databáze: OpenAIRE