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Quantitative, multiplexed, targeted proteomics for ascertaining variant specific SARS-CoV-2 antibody response.

Ivan Doykov1,2, Tomas Baldwin1, Justyna Spiewak1

  • 1Translational Mass Spectrometry Research Group, Genetics & Genomic Medicine Department, UCL Institute of Child Health, London, UK.

Cell Reports Methods
|August 17, 2022
PubMed
Summary

A new proteomics assay accurately measures immune responses to SARS-CoV-2 variants of concern (VoCs). This method reveals altered antibody and complement activity against VoCs, with Omicron showing a reduced response.

Keywords:
COVID-19SARS-CoV-2complement: immunoglobulindelta variantmass spectrometryomicron variantproteomicsvaccinationvariant of concern

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Area of Science:

  • Immunology
  • Virology
  • Proteomics

Background:

  • Assessing immunity to SARS-CoV-2 variants of concern (VoCs) is vital for public health.
  • Existing serological assays have limitations in comprehensively evaluating immune responses.

Purpose of the Study:

  • To develop a novel multiplexed proteomics assay for direct detection of antibodies and immunocomplexes against SARS-CoV-2 spike proteins.
  • To evaluate immune responses to various SARS-CoV-2 VoCs, including Alpha, Beta, Delta, and Omicron.

Main Methods:

  • Utilized multiplexed, targeted proteomics to detect multiple proteins in SARS-CoV-2 anti-spike antibody immunocomplexes.
  • Analyzed serum samples from individuals with prior infection or vaccination.
  • Correlated assay results with existing serology and neutralization assays.

Main Results:

  • The assay demonstrated concordance with existing serology and neutralization methods.
  • Observed altered immunoglobulin and complement responses to Alpha, Beta, and Delta VoCs.
  • Detected a reduced immune response to the Omicron VoC.
  • Identified a strong association between C1q and IgG1, potentially reflecting neutralization capacity.

Conclusions:

  • The developed proteomics assay provides a more informative assessment of immune responses to SARS-CoV-2 VoCs compared to traditional ELISA.
  • Analyzing immunoproteins beyond IgG offers deeper insights into infection and vaccination responses.
  • This approach aids in immune surveillance and vaccine development against evolving viral threats.