Skip to Content
MilliporeSigma
  • Profiling B cell immunodominance after SARS-CoV-2 infection reveals antibody evolution to non-neutralizing viral targets.

Profiling B cell immunodominance after SARS-CoV-2 infection reveals antibody evolution to non-neutralizing viral targets.

Immunity (2021-05-23)
Haley L Dugan, Christopher T Stamper, Lei Li, Siriruk Changrob, Nicholas W Asby, Peter J Halfmann, Nai-Ying Zheng, Min Huang, Dustin G Shaw, Mari S Cobb, Steven A Erickson, Jenna J Guthmiller, Olivia Stovicek, Jiaolong Wang, Emma S Winkler, Maria Lucia Madariaga, Kumaran Shanmugarajah, Maud O Jansen, Fatima Amanat, Isabelle Stewart, Henry A Utset, Jun Huang, Christopher A Nelson, Ya-Nan Dai, Paige D Hall, Robert P Jedrzejczak, Andrzej Joachimiak, Florian Krammer, Michael S Diamond, Daved H Fremont, Yoshihiro Kawaoka, Patrick C Wilson
ABSTRACT

Dissecting the evolution of memory B cells (MBCs) against SARS-CoV-2 is critical for understanding antibody recall upon secondary exposure. Here, we used single-cell sequencing to profile SARS-CoV-2-reactive B cells in 38 COVID-19 patients. Using oligo-tagged antigen baits, we isolated B cells specific to the SARS-CoV-2 spike, nucleoprotein (NP), open reading frame 8 (ORF8), and endemic human coronavirus (HCoV) spike proteins. SARS-CoV-2 spike-specific cells were enriched in the memory compartment of acutely infected and convalescent patients several months post symptom onset. With severe acute infection, substantial populations of endemic HCoV-reactive antibody-secreting cells were identified and possessed highly mutated variable genes, signifying preexisting immunity. Finally, MBCs exhibited pronounced maturation to NP and ORF8 over time, especially in older patients. Monoclonal antibodies against these targets were non-neutralizing and non-protective in vivo. These findings reveal antibody adaptation to non-neutralizing intracellular antigens during infection, emphasizing the importance of vaccination for inducing neutralizing spike-specific MBCs.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Human IgA (α-chain specific)−Peroxidase antibody produced in goat, affinity isolated antibody
Sigma-Aldrich
Anti-Human IgM (μ-chain specific)−Peroxidase antibody produced in goat, affinity isolated antibody, buffered aqueous solution
Sigma-Aldrich
Anti-Human IgG (Fab specific)−Peroxidase antibody produced in goat, affinity isolated antibody
Sigma-Aldrich
Lipopolysaccharides from Escherichia coli O55:B5, purified by phenol extraction
Sigma-Aldrich
Insulin human, recombinant, expressed in yeast (proprietary host)