Effects of Prior Infection with SARS-CoV-2 on B Cell Receptor Repertoire Response during Vaccination

Elizabeth R Fraley; Santosh Khanal; Stephen H Pierce; Cas A LeMaster; Rebecca McLennan; Tomi Pastinen; Todd Bradley

doi:10.3390/vaccines10091477

Effects of Prior Infection with SARS-CoV-2 on B Cell Receptor Repertoire Response during Vaccination

Vaccines (Basel). 2022 Sep 6;10(9):1477. doi: 10.3390/vaccines10091477.

Authors

Elizabeth R Fraley¹, Santosh Khanal¹, Stephen H Pierce^{1

2}, Cas A LeMaster¹, Rebecca McLennan¹, Tomi Pastinen^{1

3}, Todd Bradley^{1

2

3

4}

Affiliations

¹ Genomic Medicine Center, Children's Mercy Research Institute, Children's Mercy Kansas City, Kansas City, MO 64108, USA.
² Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66160, USA.
³ Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108, USA.
⁴ Department of Pediatrics, University of Kansas Medical Center, Kansas City, KS 66160, USA.

Abstract

Understanding the B cell response to SARS-CoV-2 vaccines is a high priority. High-throughput sequencing of the B cell receptor (BCR) repertoire allows for dynamic characterization of B cell response. Here, we sequenced the BCR repertoire of individuals vaccinated by the Pfizer SARS-CoV-2 mRNA vaccine. We compared BCR repertoires of individuals with previous COVID-19 infection (seropositive) to individuals without previous infection (seronegative). We discovered that vaccine-induced expanded IgG clonotypes had shorter heavy-chain complementarity determining region 3 (HCDR3), and for seropositive individuals, these expanded clonotypes had higher somatic hypermutation (SHM) than seronegative individuals. We uncovered shared clonotypes present in multiple individuals, including 28 clonotypes present across all individuals. These 28 shared clonotypes had higher SHM and shorter HCDR3 lengths compared to the rest of the BCR repertoire. Shared clonotypes were present across both serotypes, indicating convergent evolution due to SARS-CoV-2 vaccination independent of prior viral exposure.

Keywords: B cell receptor heavy-chain sequencing; SARS-CoV-2; vaccine response.

Grants and funding

Funding for this work was through internal institutional funds to T.B. from Children’s Mercy Research Institute and Children’s Mercy Kansas City. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.