Abstract

Dendritic cells (DCs) facilitate cross talk between the innate and adaptive immune system. They sense and phagocytose invading pathogens, and are not only capable of activating naïve T cells, but can also determine the polarization of T cell responses into different effector subtypes. Polarized T cells in turn have a crucial role in antibody class switching and affinity maturation, and consequently the quality of the resulting humoral immunity. Targeting vaccines to DCs thus provides a great deal of opportunities for influencing the humoral immune responses, by fine-tuning the T cell response as well as regulating antigen availability for B cells. In this review we aim to outline how different DC targeted vaccination strategies can be utilized to induce a desired humoral immune response. A range of factors, including route of vaccine administration, use of adjuvants, choice of DC subset and surface receptor to target have been reported to influence the resulting immune response and will be reviewed herein. Finally, we will discuss opportunities for designing improved vaccines and challenges with translating this knowledge into clinical or veterinary medicine.

Highlights

  • Conventional dendritic cells are divided into two sub-populations, cDC1s and cDC2s, based on ontogenic and functional differences [reviewed in [1, 2]]

  • Both cDC1s and cDC2s can present antigen-derived peptides on MHC-II to CD4+ T cells, studies have reported that cDC2s are more efficient at this process [12, 13]

  • Dendritic cells (DCs) targeting strategies aiming to achieve good antibody responses should be designed with the B cell antigen availability kinetics in mind, whether they are based on DNA or protein immunization

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Summary

INTRODUCTION

Conventional dendritic cells (cDCs) are divided into two sub-populations, cDC1s and cDC2s, based on ontogenic and functional differences [reviewed in [1, 2]]. Differentiation into cDC1s is dependent on the transcription factors IRF8 [6] and Id2 [7], and to a lesser extent BATF3 [8, 9], while cDC2 differentiation is dependent on IRF4 [10, 11] Both cDC1s and cDC2s can present antigen-derived peptides on MHC-II to CD4+ T cells, studies have reported that cDC2s are more efficient at this process [12, 13]. We review the current literature on how delivering antigens to cDCs can be utilized to enhance both the polarization and the magnitude of the humoral response, and discuss how different immunization strategies can be utilized to fine-tune the antibody responses

ANTIBODY POLARIZATION AS A FUNCTION OF DC SUBTYPE
TARGETING DIFFERENT DC RECEPTORS IMPACTS ANTIBODY POLARIZATION
MAGNITUDE OF THE ANTIBODY RESPONSE
MODULATING ANTIGEN AVAILABILITY KINETICS TO INCREASE ANTIBODY RESPONSES
TRANSLATION TO CLINICAL MEDICINE
CONCLUDING REMARKS
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