A system-view of Bordetella pertussis booster vaccine responses in adults primed with whole-cell versus acellular vaccine in infancy

JCI Insight. 2021 Apr 8;6(7):e141023. doi: 10.1172/jci.insight.141023.


The increased incidence of whooping cough worldwide suggests that current vaccination against Bordetella pertussis infection has limitations in quality and duration of protection. The resurgence of infection has been linked to the introduction of acellular vaccines (aP), which have an improved safety profile compared with the previously used whole-cell (wP) vaccines. To determine immunological differences between aP and wP priming in infancy, we performed a systems approach of the immune response to booster vaccination. Transcriptomic, proteomic, cytometric, and serologic profiling revealed multiple shared immune responses with different kinetics across cohorts, including an increase of blood monocyte frequencies and strong antigen-specific IgG responses. Additionally, we found a prominent subset of aP-primed individuals (30%) with a strong differential signature, including higher levels of expression for CCL3, NFKBIA, and ICAM1. Contrary to the wP individuals, this subset displayed increased PT-specific IgE responses after boost and higher antigen-specific IgG4 and IgG3 antibodies against FHA and FIM2/3 at baseline and after boost. Overall, the results show that, while broad immune response patterns to Tdap boost overlap between aP- and wP-primed individuals, a subset of aP-primed individuals present a divergent response. These findings provide candidate targets to study the causes and correlates of waning immunity after aP vaccination.

Keywords: Bacterial vaccines; Immunology; Imprinting; Vaccines.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antibodies, Bacterial / blood
  • Antibodies, Bacterial / immunology
  • Bordetella pertussis / immunology
  • Chemokine CCL3 / genetics
  • Chemokine CCL3 / immunology
  • Cytokines / blood
  • Cytokines / immunology
  • Gene Expression / drug effects
  • Humans
  • Immunity, Humoral / drug effects*
  • Immunization, Secondary*
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / immunology
  • NF-KappaB Inhibitor alpha / genetics
  • NF-KappaB Inhibitor alpha / immunology
  • Neutrophils / drug effects*
  • Neutrophils / immunology
  • Neutrophils / physiology
  • Pertussis Vaccine / immunology*
  • Pertussis Vaccine / pharmacology
  • Vaccines, Acellular / immunology
  • Vaccines, Acellular / pharmacology


  • Antibodies, Bacterial
  • CCL3 protein, human
  • Chemokine CCL3
  • Cytokines
  • ICAM1 protein, human
  • NFKBIA protein, human
  • Pertussis Vaccine
  • Vaccines, Acellular
  • Intercellular Adhesion Molecule-1
  • NF-KappaB Inhibitor alpha