Mass spectrometric analysis of multiple pertussis toxins and toxoids

Yulanda M Williamson1, Hercules Moura, David Schieltz

  • 1Biological Mass Spectrometry Laboratory, National Center for Environmental Health, Centers for Disease Control and Prevention, Chamblee, GA 30341, USA.

Insights

This study analyzed pertussis toxin (Ptx) from vaccines using mass spectrometry. Findings show similarities in Ptx subunits but also differences in their relative amounts, potentially impacting immune response to pertussis.

Area of Science:

  • Microbiology
  • Immunology
  • Analytical Chemistry

Background:

  • Pertussis, caused by Bordetella pertussis (Bp), is a rising concern, particularly in children.
  • Current acellular pertussis vaccines contain pertussis toxin (Ptx), a key virulence factor.
  • Variations in Ptx subunit amino acid (AA) sequences may influence vaccine efficacy and immune response.

Purpose of the Study:

  • To comparatively analyze Ptx and its toxoid (Ptxd) from commercial sources and licensed vaccines.
  • To assess variability in peptide sequence, AA coverage, and relative subunit abundance.
  • To investigate potential impacts of Ptx variations on immune responses.

Main Methods:

  • Blind comparative mass spectrometric (MS) analysis.
  • Assessment of peptide sequence and AA coverage.
  • Label-free mass spectrometry-based quantification for relative subunit abundance.

Main Results:

  • Qualitative similarities were observed across Ptx sources regarding AA percent coverages and MS/MS fragmentation profiles.
  • Quantitative analysis revealed differential relative abundance of Ptx subunits among the analyzed sources.
  • Variability in Ptx subunit composition was identified between commercial Ptx and vaccine-derived Ptxd.

Conclusions:

  • While Ptx subunits show qualitative similarities, quantitative differences in their abundance exist.
  • These variations in Ptx composition may have implications for the immunogenicity and effectiveness of pertussis vaccines.
  • Further research is warranted to understand the functional consequences of observed Ptx variations.

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