Atypical B cells and impaired SARS-CoV-2 neutralization following heterologous vaccination in the elderly

Isabella A T M Ferreira¹, Colin Y C Lee², William S Foster³, Adam Abdullahi¹, Lisa M Dratva⁴, Zewen Kelvin Tuong², Benjamin J Stewart², John R Ferdinand⁵, Stephane M Guillaume³, Martin O P Potts¹, Marianne Perera¹, Benjamin A Krishna¹, Ana Peñalver⁵, Mia Cabantous⁵, Steven A Kemp¹, Lourdes Ceron-Gutierrez⁶, Soraya Ebrahimi⁶; CITIID-NIHR BioResource COVID-19 Collaboration; Paul Lyons¹, Kenneth G C Smith¹, John Bradley¹, Dami A Collier¹, Laura E McCoy⁷, Agatha van der Klaauw⁸, James E D Thaventhiran⁹, I Sadaf Farooqi⁸, Sarah A Teichmann⁴, Paul A MacAry¹⁰, Rainer Doffinger⁶, Mark R Wills¹, Michelle A Linterman¹¹, Menna R Clatworthy¹², Ravindra K Gupta¹³

Affiliations

¹ Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK.
² Molecular Immunity Unit, Department of Medicine, Medical Research Council Laboratory of Molecular Biology, University of Cambridge, Cambridge, UK; Cellular Genetics, Wellcome Sanger Institute, Cambridge, UK.
³ Immunology Programme, Babraham Institute, Babraham Research Campus, Cambridge, UK.
⁴ Cellular Genetics, Wellcome Sanger Institute, Cambridge, UK.
⁵ Molecular Immunity Unit, Department of Medicine, Medical Research Council Laboratory of Molecular Biology, University of Cambridge, Cambridge, UK.
⁶ Department of Clinical Biochemistry and Immunology, Cambridge University Hospital NHS Trust, Cambridge, UK.
⁷ Division of Infection and Immunity, UCL, London, UK.
⁸ University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Wellcome-Medical Research Council (MRC) Institute of Metabolic Science, Cambridge, UK.
⁹ MRC Toxicology Unit, University of Cambridge, Cambridge, UK.
¹⁰ National University of Singapore, Singapore, Singapore.
¹¹ Immunology Programme, Babraham Institute, Babraham Research Campus, Cambridge, UK. Electronic address: michelle.linterman@babraham.ac.uk.
¹² Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK; Molecular Immunity Unit, Department of Medicine, Medical Research Council Laboratory of Molecular Biology, University of Cambridge, Cambridge, UK; Cellular Genetics, Wellcome Sanger Institute, Cambridge, UK. Electronic address: mrc38@medschl.cam.ac.uk.
¹³ Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK. Electronic address: rkg20@cam.ac.uk.

PMID: 37590132
DOI: 10.1016/j.celrep.2023.112991

Free article

Atypical B cells and impaired SARS-CoV-2 neutralization following heterologous vaccination in the elderly

Isabella A T M Ferreira et al. Cell Rep. 2023.

Free article

. 2023 Aug 29;42(8):112991.

doi: 10.1016/j.celrep.2023.112991. Epub 2023 Aug 16.

Authors

Affiliations

¹ Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK.
² Molecular Immunity Unit, Department of Medicine, Medical Research Council Laboratory of Molecular Biology, University of Cambridge, Cambridge, UK; Cellular Genetics, Wellcome Sanger Institute, Cambridge, UK.
³ Immunology Programme, Babraham Institute, Babraham Research Campus, Cambridge, UK.
⁴ Cellular Genetics, Wellcome Sanger Institute, Cambridge, UK.
⁵ Molecular Immunity Unit, Department of Medicine, Medical Research Council Laboratory of Molecular Biology, University of Cambridge, Cambridge, UK.
⁶ Department of Clinical Biochemistry and Immunology, Cambridge University Hospital NHS Trust, Cambridge, UK.
⁷ Division of Infection and Immunity, UCL, London, UK.
⁸ University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Wellcome-Medical Research Council (MRC) Institute of Metabolic Science, Cambridge, UK.
⁹ MRC Toxicology Unit, University of Cambridge, Cambridge, UK.
¹⁰ National University of Singapore, Singapore, Singapore.
¹¹ Immunology Programme, Babraham Institute, Babraham Research Campus, Cambridge, UK. Electronic address: michelle.linterman@babraham.ac.uk.
¹² Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK; Molecular Immunity Unit, Department of Medicine, Medical Research Council Laboratory of Molecular Biology, University of Cambridge, Cambridge, UK; Cellular Genetics, Wellcome Sanger Institute, Cambridge, UK. Electronic address: mrc38@medschl.cam.ac.uk.
¹³ Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK. Electronic address: rkg20@cam.ac.uk.

PMID: 37590132
DOI: 10.1016/j.celrep.2023.112991

Abstract

Suboptimal responses to a primary vaccination course have been reported in the elderly, but there is little information regarding the impact of age on responses to booster third doses. Here, we show that individuals 70 years or older (median age 73, range 70-75) who received a primary two-dose schedule with AZD1222 and booster third dose with mRNA vaccine achieve significantly lower neutralizing antibody responses against SARS-CoV-2 spike pseudotyped virus compared with those younger than 70 (median age 66, range 54-69) at 1 month post booster. Impaired neutralization potency and breadth post third dose in the elderly is associated with circulating "atypical" spike-specific B cells expressing CD11c and FCRL5. However, when considering individuals who received three doses of mRNA vaccine, we did not observe differences in neutralization or enrichment in atypical B cells. This work highlights the finding that AdV and mRNA COVID-19 vaccine formats differentially instruct the memory B cell response.

Keywords: AZD1222; BNT162b2; CP: Immunology; SARS-CoV-2; elderly.

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Conflict of interest statement

Declaration of interests R.K.G. has received honoraria for consulting and educational activities from Gilead, GSK, Janssen, and Moderna.

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Atypical B cells and impaired SARS-CoV-2 neutralization following heterologous vaccination in the elderly

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Atypical B cells and impaired SARS-CoV-2 neutralization following heterologous vaccination in the elderly

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