Effects of commonly used antiviral vaccines on human plasmacytoid dendritic cells

Abstract

Human plasmacytoid dendritic cells (pDCs) represent a special subset of immune cells that play an important role in antiviral immunity by stimulating T cell responses and linking the innate and adaptive immune system. Despite their well-recognised antiviral role, little is known about the contribution of pDCs to vaccine-induced immunity. Beside their immunogenic functions, pDCs are also capable to suppress T cell proliferation e.g. by secretion of granzyme B (GrB). However, the regulation of pDC-derived GrB has rarely been investigated so far. This study analysed the effects of commonly used antiviral vaccines against polio, measles, yellow fever, rubella and tick-borne encephalitis on pDCs with a special focus on GrB. Expression and secretion of GrB by pDCs decreased upon stimulation with all tested vaccines. Furthermore, tick-borne encephalitis vaccine (TBEV) as one of the strongest suppressors of GrB inhibited transfer of GrB to T cells. In contrast to the general influence of the vaccines on pDC-derived GrB, only TBEV induced substantial secretion of interferon-alpha (IFN-alpha) and the expression of the costimulatory surface molecule cluster of differentiation (CD)86. Despite the immunostimulatory effects of the vaccines, the potential of pDCs to stimulate T cell proliferation was only weakly modulated. The immunogenic influence of the vaccines on pDCs demonstrated in the present study argues for a direct contribution of pDCs to vaccine-induced immune responses. Hence, these vaccines might be used as clinically available, activating agents for pDCs and other dendritic cells in the context of immunotherapeutic approaches, e.g. anticancer vaccines. The inhibitory effect of the vaccines on immunosuppressive pDC-derived GrB suggests a novel mechanism of how commonly used antiviral vaccines influence the immune system and suggests the evaluation of novel GrB inhibitors as vaccine adjuvants.