Tracking B cell responses to the SARS-CoV-2 mRNA-1273 vaccine
Felipe Lopes de Assis,
Kenneth B. Hoehn,
Xiaozhen Zhang,
Lela Kardava,
Connor D. Smith,
Omar El Merhebi,
Clarisa M. Buckner,
Krittin Trihemasava,
Wei Wang,
Catherine A. Seamon,
Vicky Chen,
Paul Schaughency,
Foo Cheung,
Andrew J. Martins,
Chi-I Chiang,
Yuxing Li,
John S. Tsang,
Tae-Wook Chun,
Steven H. Kleinstein,
Susan Moir
Affiliations
Felipe Lopes de Assis
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Kenneth B. Hoehn
Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA
Xiaozhen Zhang
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Lela Kardava
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Connor D. Smith
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Omar El Merhebi
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Clarisa M. Buckner
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Krittin Trihemasava
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Wei Wang
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Catherine A. Seamon
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Vicky Chen
Integrated Data Sciences Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Paul Schaughency
Integrated Data Sciences Section, Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Foo Cheung
NIH Center for Human Immunology, NIAID, NIH, Bethesda, MD 20892, USA
Andrew J. Martins
Multiscale Systems Biology Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD 20892, USA
Chi-I Chiang
Institute for Bioscience and Biotechnology Research, Rockville, MD 20850, USA
Yuxing Li
Institute for Bioscience and Biotechnology Research, Rockville, MD 20850, USA; Department of Microbiology and Immunology and Center for Biomolecular Therapeutics, University of Maryland School of Medicine, Baltimore, MD 21201, USA
John S. Tsang
NIH Center for Human Immunology, NIAID, NIH, Bethesda, MD 20892, USA; Multiscale Systems Biology Section, Laboratory of Immune System Biology, NIAID, NIH, Bethesda, MD 20892, USA
Tae-Wook Chun
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Steven H. Kleinstein
Department of Pathology, Yale School of Medicine, New Haven, CT 06520, USA; Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT 06511, USA; Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA
Susan Moir
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA; Corresponding author
Summary: Protective immunity following vaccination is sustained by long-lived antibody-secreting cells and resting memory B cells (MBCs). Responses to two-dose SARS-CoV-2 mRNA-1273 vaccination are evaluated longitudinally by multimodal single-cell analysis in three infection-naïve individuals. Integrated surface protein, transcriptomics, and B cell receptor (BCR) repertoire analysis of sorted plasmablasts and spike+ (S-2P+) and S-2P− B cells reveal clonal expansion and accumulating mutations among S-2P+ cells. These cells are enriched in a cluster of immunoglobulin G-expressing MBCs and evolve along a bifurcated trajectory rooted in CXCR3+ MBCs. One branch leads to CD11c+ atypical MBCs while the other develops from CD71+ activated precursors to resting MBCs, the dominant population at month 6. Among 12 evolving S-2P+ clones, several are populated with plasmablasts at early timepoints as well as CD71+ activated and resting MBCs at later timepoints, and display intra- and/or inter-cohort BCR convergence. These relationships suggest a coordinated and predictable evolution of SARS-CoV-2 vaccine-generated MBCs.
