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Th1/Th17 polarization persists following whole-cell pertussis vaccination despite repeated acellular boosters
Ricardo da Silva Antunes, … , Bjoern Peters, Alessandro Sette
Ricardo da Silva Antunes, … , Bjoern Peters, Alessandro Sette
Published June 19, 2018
Citation Information: J Clin Invest. 2018;128(9):3853-3865. https://doi.org/10.1172/JCI121309.
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Research Article Immunology Vaccines

Th1/Th17 polarization persists following whole-cell pertussis vaccination despite repeated acellular boosters

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Abstract

In the mid-1990s, whole-cell pertussis (wP) vaccines were associated with local and systemic adverse events that prompted their replacement with acellular pertussis (aP) vaccines in many high-income countries. In the past decade, rates of pertussis disease have increased in children receiving only aP vaccines. We compared the immune responses to aP boosters in individuals who received their initial doses with either wP or aP vaccines using activation-induced marker (AIM) assays. Specifically, we examined pertussis-specific memory CD4+ T cell responses ex vivo, highlighting a type 2/Th2 versus type 1/Th1 and Th17 differential polarization as a function of childhood vaccination. Remarkably, after a contemporary aP booster, cells from donors originally primed with aP were (a) associated with increased IL-4, IL-5, IL-13, IL-9, and TGF-β and decreased IFN-γ and IL-17 production, (b) defective in their ex vivo capacity to expand memory cells, and (c) less capable of proliferating in vitro. These differences appeared to be T cell specific, since equivalent increases of antibody titers and plasmablasts after aP boost were seen in both groups. In conclusion, our data suggest that there are long-lasting effects and differences in polarization and proliferation of T cell responses in adults originally vaccinated with aP compared with those that initially received wP, despite repeated acellular boosters.

Authors

Ricardo da Silva Antunes, Mariana Babor, Chelsea Carpenter, Natalie Khalil, Mario Cortese, Alexander J. Mentzer, Grégory Seumois, Christopher D. Petro, Lisa A. Purcell, Pandurangan Vijayanand, Shane Crotty, Bali Pulendran, Bjoern Peters, Alessandro Sette

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Figure 8

Some, but not all, alterations extend to TT-specific responses.

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Some, but not all, alterations extend to TT-specific responses.
(A) Perc...
(A) Percentage of TT-specific CD4+ T cell subsets gated in AIM25+ cells before or following boost. Each dot represents 1 donor followed longitudinally (n = 17 for aP and n = 14 for wP cohorts). Wilcoxon’s paired t test. (B) Longitudinal kinetics of PT-specific CD4+ T cell responses after boost represented as fold increase of the percentage of AIM25+ cells to nonboost responses for aP- or wP-primed cohorts. Data are expressed as median ± the interquartile range for each cohort (n = 18 for aP and n = 17 for wP cohorts). (C). Ab titers for TT toxoid antigen in respective cohorts (n = 19 for aP and n = 14 for wP cohorts). Response before and after boost vaccine analyzed via Wilcoxon’s paired t test. (D) Total TT-specific CD4+ T cell number response after AIM25 assay to each indicated cytokine. Each dot represents 1 donor (n = 23 for each cohort). P value is shown as statistically significant by 2-tailed Mann-Whitney U test. (E) Percentage of TT-specific CD4+ T cells after 6 days of CFSE assay. Results are presented as median ± interquartile range (n = 20 for each cohort).
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