Abstract
Vaccine development is an expensive and time-consuming process that heavily relies on animal models. Yet, vaccine candidates that have previously succeeded in animal experiments often fail in clinical trials questioning the predictive value of animal models. Alternative assay systems that can add to the screening and evaluation of functional characteristics of vaccines in a human context before embarking on costly clinical trials are therefore urgently needed. In this study, we have established an in vitro system consisting of long-term cultures of unfractionated peripheral blood mononuclear cells (PBMCs) from healthy volunteers to assess (recall) T cell responses to vaccine candidates. We observed that different types of influenza vaccines (whole inactivated virus (WIV), split, and peptide vaccines) were all able to stimulate CD4 and CD8 T cell responses but to different extents in line with their reported in vivo properties. In-depth analyses of different T cell subsets revealed that the tested vaccines evoked mainly recall responses as indicated by the fact that the vast majority of the responding T cells had a memory phenotype. Furthermore, we observed vaccine-induced activation of T follicular helper cells, which are associated with the induction of humoral immune responses. Our results demonstrate the suitability of the established PBMC-based system for the in vitro evaluation of memory T cell responses to vaccines and the comparison of vaccine candidates in a human immune cell context. As such, it can help to bridge the gap between animal experiments and clinical trials and assist in the selection of promising vaccine candidates, at least for recall antigens.
Highlights
Vaccination is the primary measure for the control of infectious diseases and, in light of increasing resistance of microorganisms to antimicrobial treatment, might even gain more importance in the future.Yet, vaccine development is an expensive and time-consuming process with only a few successful outcomes
We demonstrated that primary human monocyte-derived dendritic cells (DCs) respond to different types of influenza vaccines in qualitatively and quantitatively characteristic ways, in line with the known in vivo properties of these vaccine types [4]
To establish a peripheral blood mononuclear cells (PBMCs)-based system to assess vaccine-induced T cell responses in vitro, we first set out to understand the kinetics of the T cell responses over time
Summary
Vaccination is the primary measure for the control of infectious diseases and, in light of increasing resistance of microorganisms to antimicrobial treatment, might even gain more importance in the future. Vaccine development is an expensive and time-consuming process with only a few successful outcomes. During vaccine development, monitoring vaccine immunogenicity represents a key step that, to date, essentially relies on animal testing. The predictive value of small animal models for the situation in humans is often poor due to intrinsic differences between the immune systems and very different immune biographies [1]. Numerous vaccine candidates that succeeded in animal experiments subsequently performed poorly in clinical trials [2,3]. Frequent failure of vaccines during expensive clinical trials highlights the need for innovative experimental
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