Targeting dendritic cells: a promising strategy to improve vaccine effectiveness

Abstract

Dendritic cell (DC) targeting is a novel strategy to enhance vaccination efficacy. This approach is based on the in situ delivery of antigen via antibodies that are specific for endocytic receptors expressed at the surface of DCs. Here we review the complexity of the DC subsets and the antigen presentation pathways that need to be considered in the settings of DC targeting. We also summarize current knowledge about antigen delivery to DCs via DEC-205, Clec9A and Clec12A, receptor targets that strongly enhance cellular and humoral immune responses. Finally, we discuss the intracellular trafficking criteria of the targeted receptors that may impact their effectiveness as DC targets.

Figure 1

Immune responses elicited by antigen targeting to DEC-205. Adjuvant-free immunization of mice with antigen-conjugated anti-DEC-205 antibodies leads to regulatory T-cell-dependent tolerance. In contrast, co-injection of an adjuvant with anti-DEC-205 primes a robust cytotoxic T-cell immune response. It also strongly activates a CD4⁺ T-cell immune response leading to generation of T_h cells that support the humoral response.

Figure 2

Immune responses elicited by antigen targeting to Clec9A. At steady state, some antigen-conjugated anti-Clec9A antibodies generate regulatory T cells that lead to tolerance. Alternatively, other anti-Clec9A antibodies activate a robust humoral response that involves the production of T_fh. Antigen delivery to DCs via Clec9A also elicits a strong CTL immune response that requires adjuvant administration.