Cell Reports (Aug 2023)
Atypical B cells and impaired SARS-CoV-2 neutralization following heterologous vaccination in the elderly
- Isabella A.T.M. Ferreira,
- Colin Y.C. Lee,
- William S. Foster,
- Adam Abdullahi,
- Lisa M. Dratva,
- Zewen Kelvin Tuong,
- Benjamin J. Stewart,
- John R. Ferdinand,
- Stephane M. Guillaume,
- Martin O.P. Potts,
- Marianne Perera,
- Benjamin A. Krishna,
- Ana Peñalver,
- Mia Cabantous,
- Steven A. Kemp,
- Lourdes Ceron-Gutierrez,
- Soraya Ebrahimi,
- Paul Lyons,
- Kenneth G.C. Smith,
- John Bradley,
- Dami A. Collier,
- Laura E. McCoy,
- Agatha van der Klaauw,
- James E.D. Thaventhiran,
- I. Sadaf Farooqi,
- Sarah A. Teichmann,
- Paul A. MacAry,
- Rainer Doffinger,
- Mark R. Wills,
- Michelle A. Linterman,
- Menna R. Clatworthy,
- Ravindra K. Gupta
Affiliations
- Isabella A.T.M. Ferreira
- Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK
- Colin Y.C. Lee
- 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
- William S. Foster
- Immunology Programme, Babraham Institute, Babraham Research Campus, Cambridge, UK
- Adam Abdullahi
- Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK
- Lisa M. Dratva
- Cellular Genetics, Wellcome Sanger Institute, Cambridge, UK
- Zewen Kelvin Tuong
- 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
- Benjamin J. Stewart
- 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
- John R. Ferdinand
- Molecular Immunity Unit, Department of Medicine, Medical Research Council Laboratory of Molecular Biology, University of Cambridge, Cambridge, UK
- Stephane M. Guillaume
- Immunology Programme, Babraham Institute, Babraham Research Campus, Cambridge, UK
- Martin O.P. Potts
- Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK
- Marianne Perera
- Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK
- Benjamin A. Krishna
- Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK
- Ana Peñalver
- Molecular Immunity Unit, Department of Medicine, Medical Research Council Laboratory of Molecular Biology, University of Cambridge, Cambridge, UK
- Mia Cabantous
- Molecular Immunity Unit, Department of Medicine, Medical Research Council Laboratory of Molecular Biology, University of Cambridge, Cambridge, UK
- Steven A. Kemp
- Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK
- Lourdes Ceron-Gutierrez
- Department of Clinical Biochemistry and Immunology, Cambridge University Hospital NHS Trust, Cambridge, UK
- Soraya Ebrahimi
- Department of Clinical Biochemistry and Immunology, Cambridge University Hospital NHS Trust, Cambridge, UK
- Paul Lyons
- Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK
- Kenneth G.C. Smith
- Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK
- John Bradley
- Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK
- Dami A. Collier
- Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK
- Laura E. McCoy
- Division of Infection and Immunity, UCL, London, UK
- Agatha van der Klaauw
- University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Wellcome-Medical Research Council (MRC) Institute of Metabolic Science, Cambridge, UK
- James E.D. Thaventhiran
- MRC Toxicology Unit, University of Cambridge, Cambridge, UK
- I. Sadaf Farooqi
- University of Cambridge Metabolic Research Laboratories and NIHR Cambridge Biomedical Research Centre, Wellcome-Medical Research Council (MRC) Institute of Metabolic Science, Cambridge, UK
- Sarah A. Teichmann
- Cellular Genetics, Wellcome Sanger Institute, Cambridge, UK
- Paul A. MacAry
- National University of Singapore, Singapore, Singapore
- Rainer Doffinger
- Department of Clinical Biochemistry and Immunology, Cambridge University Hospital NHS Trust, Cambridge, UK
- Mark R. Wills
- Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK
- Michelle A. Linterman
- Immunology Programme, Babraham Institute, Babraham Research Campus, Cambridge, UK; Corresponding author
- Menna R. Clatworthy
- 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; Corresponding author
- Ravindra K. Gupta
- Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK; Corresponding author
- Journal volume & issue
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Vol. 42,
no. 8
p. 112991
Abstract
Summary: 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.
