Prediction and characterisation of the human B cell response to a heterologous two-dose Ebola vaccine.

Journal: Nature communications
Published Date:

Abstract

Ebola virus disease (EVD) outbreaks are increasing, posing significant threats to affected communities. Effective outbreak management depends on protecting frontline health workers, a key focus of EVD vaccination strategies. IgG specific to the viral glycoprotein serves as the correlate of protection for recent vaccine licensures. Using advanced cellular and transcriptomic analyses, we examined B cell responses to the Ad26.ZEBOV, MVA-BN-Filo EVD vaccine. Our findings reveal robust plasma cell and lasting B cell memory responses post-vaccination. Machine-learning models trained on blood gene expression predicted antibody response magnitude. Notably, we identified a unique B cell receptor CDRH3 sequence post-vaccination resembling known Orthoebolavirus zairense (EBOV) glycoprotein-binding antibodies. Single-cell analyses further detailed changes in plasma cell frequency, subclass usage, and CDRH3 properties. These results highlight the predictive power of early immune responses, captured through systems immunology, in shaping vaccine-induced B cell immunity.

Authors

  • Daniel O'Connor
    Department of Radiation Oncology, University of California, Los Angeles, CA, 90095, USA.
  • Elizabeth A Clutterbuck
    Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Malick M Gibani
    Department of Infectious Disease, Imperial College London, St Mary's Campus, London, United Kingdom.
  • Sagida Bibi
    Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Katherine A Sanders
    Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Rebecca Makinson
    NIHR Oxford Biomedical Research Centre, Oxford, UK.
  • Dominic F Kelly
    Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
  • Andrew J Pollard
    Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; National Institute for Health Research, Oxford Biomedical Research Centre, Oxford, UK.