Tetanus Toxoid carrier protein induced T-helper cell responses upon vaccination of middle-aged adults

Introduction: Vaccines frequently induce suboptimal immune responses in the elderly, due to immunological ageing. Timely vaccination may be a strategy to overcome this problem, which classifies middle-aged adults as an interesting target group for future vaccine interventions. However, the immunological fitness of the middle-aged population is ill-defined. It is currently unknown whether effective T-cell help towards B-cells is initiated by conjugate-carrier vaccines at middle-age. Aim: We characterized systemic Tetanus Toxoid (TT) specific T-helper cell responses in the circulation of middle-aged adults (50-65 years of age, n = 31) having received the MenACWY-TT vaccination. Methods: Blood samples were taken pre- as well as 7 days, 28 days, and 1 year post-vaccination. TT specific T-cell responses were determined by IFN gamma Elispot and by the secretion of IFN gamma, IL13, IL10, IL17, and IL21 in cell culture supernatants. Circulating CD4+CXCR5+ICOS+IL21+ cells were analyzed by flow cytometry, and meningococcal and TT-specific IgG responses by bead-based immunoassays. The correlation between the T-cell help and humoral responses was evaluated. Results: Vaccination with a TT-carrier protein induced a mixed TT-specific Th1 (IFN gamma), Th2 (IL13, IL10), and Th1 7 (IL17) response in most participants. Additionally, circulating CD4+CXCR5+ICOS+IL21+ cells were significantly increased 7 days post-vaccination. Pre-vaccination TT-specific cytokine production and post-vaccination Th2 responses correlated positively with the increase of CD4+CXCR5+ICOS+IL21+ cells. No correlation between T-cell help and antibody responses was found. Conclusion: The characteristics of the T-cell response upon a TT-carrier vaccination suggests effective T-cell help towards B-cells in response to meningococcal polysaccharides, although the absence of a "correlation with the antibody responses warrants further clarification. However, the robust T-helper cell response in middle-aged adults, decades after previous TT vaccinations, strengthens the classification of this age group for future vaccine interventions in the context of population ageing. (C) 2017 The Author(s). Published by Elsevier Ltd.