Abstract
Despite significant effort, the development of effective vaccines inducing strong and durable T-cell responses against intracellular pathogens and cancer cells has remained a challenge. The initiation of effector CD8+ T-cell responses requires the presentation of peptides derived from internalized antigen on class I major histocompatibility complex molecules by dendritic cells (DCs) in a process called cross-presentation. A current strategy to enhance the effectiveness of vaccination is to deliver antigens directly to DCs. This is done via selective targeting of antigen using monoclonal antibodies directed against endocytic receptors on the surface of the DCs. In this review, we will discuss considerations relevant to the design of such vaccines: the existence of DC subsets with specialized functions, the impact of the antigen intracellular trafficking on cross-presentation, and the influence of maturation signals received by DCs on the outcome of the immune response.
Highlights
Vaccination is the most effective way to prevent the spread of infectious diseases
A clear division of labor exists among the two myeloid DCs (mDCs) subsets in mice with CD11b− CD8α+ Dendritic cells (DCs) and CD11b− CD103+ DCs being far superior and essential at priming CD8+ T-cell responses, while CD11b+ CD8α− DCs are specialized for presenting antigen on MHCII to stimulate helper T-cell immunity [12, 46, 47]
A more direct and controlled approach to reduce unwanted systemic effects of toll-like receptors (TLR) agonists is to engineer their targeted delivery to DCs, it might affect adjuvant effectiveness if activation of bystander cells contributes to the immune response [70, 118]
Summary
Vaccination is the most effective way to prevent the spread of infectious diseases. We classify vaccines into two main types: preventative or therapeutic. Preventative vaccines typically elicit generation of specific antibodies and memory B cells They are designed to block the spread of infection through these humoral immune responses [1]. It is likely that cytotoxic CD8+ T-cell activity will be required to protect patients from these chronic conditions For this reason, efforts are required to develop carefully designed therapeutic vaccines that will derive from our increasing understanding behind the mechanisms of the human immune system. DC maturation is associated with dramatic functional and morphological changes that lead to an optimized ability to initiate T-cell immunity It is characterized by an increase in cell surface expression of MHCI and MHCII molecules and accessory/costimulatory molecules, increased antigen processing, and induction of specific cytokine production [5].
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