A system-view of Bordetella pertussis booster vaccine responses in adults primed with whole-cell versus acellular vaccine in infancy
Ricardo da Silva Antunes, … , Alessandro Sette, Bjoern Peters
Ricardo da Silva Antunes, … , Alessandro Sette, Bjoern Peters
Published March 9, 2021
Citation Information: JCI Insight. 2021;6(7):e141023. https://doi.org/10.1172/jci.insight.141023.
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Research Article Immunology Vaccines

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

Abstract

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.

Authors

Ricardo da Silva Antunes, Ferran Soldevila, Mikhail Pomaznoy, Mariana Babor, Jason Bennett, Yuan Tian, Natalie Khalil, Yu Qian, Aishwarya Mandava, Richard H. Scheuermann, Mario Cortese, Bali Pulendran, Christopher D. Petro, Adrienne P. Gilkes, Lisa A. Purcell, Alessandro Sette, Bjoern Peters

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Figure 4

Frequencies of several cell types correlate highly with gene expression levels of specific clusters.

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Frequencies of several cell types correlate highly with gene expression ...
The plots show all cell types for which Spearman’s correlations of r > 0.5 were found with a specific gene cluster — namely B cells, classical monocytes, NK cells, CD4 naive cells, ASCs, and monocytes (n = 90 equivalent to 18 individuals × 5 time points). (A) Frequency of the cell type percentages of live cells are plotted as a function of time post booster vaccination. Open circles and thin lines connecting them indicate individual responses. Closed circles and the solid lines connecting them indicate average responses over all donors. (B) Correlation of cell type frequencies with gene expression of the best-matching RNA-Seq cluster (different cluster for every cell type), quantified by the first principal component (PC1). The specific cluster is indicated on the top left corner of each plot, while its cluster group and a hallmark gene are indicated on the right.