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Atypical B cells and impaired SARS-CoV-2 neutralisation following booster vaccination in the elderly.
Isabella A.T.M. Ferreira; Colin Y.C. Lee; William Foster; Adam Abdullahi; Zewen K. Tuong; Benjamin J Stewart; John R Ferdinand; Stephane Guillaume; Martin O. P. Potts; Marianne Perera; Benjamin A Krishna; Ana P Alonso; Mia Cabantous; Steven A Kemp; Lourdes Ceron-Gutierrez; Soraya Ebrahimi; - The CITIID- NIHR BioResource COVID-19 Collaboration; Paul Lyons; Kenneth G. C. Smith; John Bradley; Dami A Collier; Sarah A Teichmann; Laura E McCoy; Paul A MacAry; Rainer Doffinger; Mark R Wills; Michelle Linterman; Menna R Clatworthy; Ravindra K Gupta.
Afiliación
  • Isabella A.T.M. Ferreira; University of Cambridge
  • Colin Y.C. Lee; Molecular Immunity Unit, Department of Medicine, Medical Research Council Laboratory of Molecular Biology, University of Cambridge, Cambridge, UK.
  • William Foster; Lymphocyte Signalling and Development, Babraham Institute, Babraham Research Campus, Cambridge, UK.
  • Adam Abdullahi; Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Cambridge, UK.
  • Zewen K. Tuong; Molecular Immunity Unit, Department of Medicine, Medical Research Council Laboratory of Molecular Biology, University of Cambridge, Cambridge, UK.
  • Benjamin J Stewart; Molecular Immunity Unit, Department of Medicine, Medical Research Council Laboratory of Molecular Biology, University of Cambridge, Cambridge, UK.
  • John R Ferdinand; Molecular Immunity Unit, Department of Medicine, Medical Research Council Laboratory of Molecular Biology, University of Cambridge, Cambridge, UK.
  • Stephane Guillaume; Lymphocyte Signalling and Development, Babraham Institute, Babraham Research Campus, Cambridge, UK.
  • Martin O. P. Potts; Department of Medicine, University of Cambridge, Cambridge, UK.
  • Marianne Perera; Department of Medicine, University of Cambridge, Cambridge, UK.
  • Benjamin A Krishna; Department of Medicine, University of Cambridge, Cambridge, UK.
  • Ana P Alonso; 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.
  • 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.
  • - The CITIID- NIHR BioResource COVID-19 Collaboration; -
  • Paul Lyons; Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Cambridge, UK.
  • Kenneth G. C. Smith; Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Cambridge, UK.
  • John Bradley; Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Cambridge, UK.
  • Dami A Collier; Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Cambridge, UK.
  • Sarah A Teichmann; Wellcome Sanger Institute, Cambridge, UK.
  • Laura E McCoy; Division of infection and immunity, UCL, London, UK
  • Paul A MacAry; National University of 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.
  • Michelle Linterman; Lymphocyte Signalling and Development, Babraham Institute, Babraham Research Campus, Cambridge, UK.
  • Menna R Clatworthy; Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Cambridge, UK.
  • Ravindra K Gupta; Cambridge Institute of Therapeutic Immunology and Infectious Disease (CITIID), Cambridge, UK.
Preprint en En | PREPRINT-MEDRXIV | ID: ppmedrxiv-22281024
ABSTRACT
Age is a major risk factor for hospitalization and death after SARS-CoV-2 infection, even in vaccinees. 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 or older who received a primary two dose schedule with AZD1222 and booster third dose with mRNA vaccine achieved significantly lower neutralizing antibody responses against SARS-CoV-2 spike pseudotyped virus compared to those younger than 70. One month after the booster neither the concentration of serum binding anti spike IgG antibody, nor the frequency of spike-specific B cells showed differences by age grouping. However, the impaired neutralization potency and breadth post-third dose in the elderly was associated with enrichment of circulating "atypical" spike-specific B cells expressing CD11c and FCRL5. Single cell RNA sequencing confirmed an expansion of TBX21-, ITGAX-expressing B cells in the elderly that enriched for B cell activation/receptor signalling pathway genes. Importantly we also observed impaired T cell responses to SARS-CoV-2 spike peptides in the elderly post-booster, both in terms of IFNgamma and IL2 secretion, as well as a decrease in T cell receptor signalling pathway genes. This expansion of atypical B cells and impaired T cell responses may contribute to the generation of less affinity-matured antibodies, with lower neutralizing capacity post-third dose in the elderly. Altogether, our data reveal the extent and potential mechanistic underpinning of the impaired vaccine responses present in the elderly after a booster dose, contributing to their increased susceptibility to COVID-19 infection.
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Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-MEDRXIV Tipo de estudio: Prognostic_studies Idioma: En Año: 2022 Tipo del documento: Preprint
Texto completo
Añadir a Mi BVS
Imprimir
XML
Buscar en Google
Texto completo: 1 Colección: 09-preprints Base de datos: PREPRINT-MEDRXIV Tipo de estudio: Prognostic_studies Idioma: En Año: 2022 Tipo del documento: Preprint