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Open AccessArticle

Uncovering Distinct Primary Vaccination-Dependent Profiles in Human Bordetella pertussis Specific CD4+ T-Cell Responses Using a Novel Whole Blood Assay

1
Center for Infectious Disease Control, National Institute for Public Health and the Environment (RIVM), 3721 MA Bilthoven, The Netherlands
2
Laboratory of Vaccinology and Mucosal Immunity, Université Libre de Bruxelles (U.L.B.), 1070 Brussels, Belgium
3
Center for Molecular and Biomolecular Informatics, Radboud Institute for Molecular Life Sciences, Radboudumc, 6525 GA Nijmegen, The Netherlands
4
Laboratory of Medical Immunology, Radboud Institute for Molecular Life Sciences, Radboudumc, 6525 GA Nijmegen, The Netherlands
*
Author to whom correspondence should be addressed.
Vaccines 2020, 8(2), 225; https://doi.org/10.3390/vaccines8020225
Received: 9 April 2020 / Revised: 6 May 2020 / Accepted: 11 May 2020 / Published: 15 May 2020
(This article belongs to the Special Issue Next-Generation Pertussis Vaccines)
To advance research and development of improved pertussis vaccines, new immunoassays are needed to qualify the outcome of Bordetella pertussis (Bp) specific CD4+ T-cell differentiation. Here, we applied a recently developed whole blood assay to evaluate Bp specific CD4+ T-cell responses. The assay is based on intracellular cytokine detection after overnight in vitro Bp antigen stimulation of diluted whole blood. We show for the first time that CD4+ T-cell memory of Th1, Th2, and Th17 lineages can be identified simultaneously in whole blood. Participants ranging from 7 to 70 years of age with different priming backgrounds of whole-cell pertussis (wP) and acellular pertussis (aP) vaccination were analyzed around an acellular booster vaccination. The assay allowed detection of low frequent antigen-specific CD4+ T-cells and revealed significantly elevated numbers of activated and cytokine-producing CD4+ T-cells, with a significant tendency to segregate recall responses based on primary vaccination background. A stronger Th2 response hallmarked an aP primed cohort compared to a wP primed cohort. In conclusion, analysis of Bp specific CD4+ T-cell responses in whole blood showed separation based on vaccination background and provides a promising tool to assess the quantity and quality of CD4+ T-cell responses induced by vaccine candidates. View Full-Text
Keywords: Bordetella pertussis; whole blood assay; CD4+ T-cells; Th polarization; Th cytokines; booster vaccination; vaccination background Bordetella pertussis; whole blood assay; CD4+ T-cells; Th polarization; Th cytokines; booster vaccination; vaccination background
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Lambert, E.E.; Corbière, V.; van Gaans-van den Brink, J.A.M.; Duijst, M.; Venkatasubramanian, P.B.; Simonetti, E.; Huynen, M.; Diavatopoulos, D.D.; Versteegen, P.; Berbers, G.A.M.; Mascart, F.; van Els, C.A.C.M. Uncovering Distinct Primary Vaccination-Dependent Profiles in Human Bordetella pertussis Specific CD4+ T-Cell Responses Using a Novel Whole Blood Assay. Vaccines 2020, 8, 225.

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