Uncovering Distinct Primary Vaccination-Dependent Profiles in Human Bordetella pertussis Specific CD4+ T-Cell Responses Using a Novel Whole Blood Assay
Eleonora E. Lambert, Véronique Corbière, Jacqueline A. M. van Gaans-van den Brink, Maxime Duijst, Prashanna Balaji Venkatasubramanian, Elles Simonetti, Martijn A. Huynen, Dimitri Diavatopoulos, Pauline Versteegen, Guy A. M. Berbers, Françoise Mascart, Cécile A. C. M. van
Abstract
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.