Antigen-presenting cells (APCs) represent a heterogeneous
population characterized by their functional specialization.
Consequently, targeting specific APC-subsets offers opportunities
to induce particular immune responses. To validate this, we
targeted lentivectors (LVs) specifically to APC-subsets using the
nanobody (Nb) display technology. This approach enables
pseudotyping of LVs by combining a binding-defective but fusogenic form of VSV.G with a membrane-bound APC-specific
Nb. Three Nbs were selected: DC1.8, R3_13 and DC2.1. The respective
LVs are referred to as DC1.8-, R3_13- and DC2.1-LVs.
Flow cytometry performed on cells obtained from in vivo transduced
murine or ex vivo transduced human lymph node cells
demonstrated that DC1.8-LVs and R3_13-LVs specifically transduced
murine and human myeloid dendritic cells (DCs) respectively.
In contrast, DC2.1-LVs transduced both human and
murine macrophages, plasmacytoid and myeloid DCs. Next we
examined the immune response elicited by intranodal immunization
of mice with ovalbumin (OVA) encoding DC1.8- or DC2.1-
LVs. DC2.1-LVs outperformed DC1.8-LVs in expansion of functional
OVA-specific CD8 T cells. Whereas the expansion of CD4 T
cells was comparable upon DC1.8- and DC2.1-LV immunization,
the cytokine profile of these CD4 T cells revealed that DC1.8-LVs
primarily induced the secretion of IL-17 and IFN-c while DC2.1-
LVs primarily induced the production of IFN-c and IL-2. This
difference in CD4 and CD8 T cell response was reflected in
therapy, demonstrating lower efficacy of DC1.8-LVs when
compared to DC2.1-LVs. In conclusion, these findings open the
perspective of a vaccination strategy that induces very particular
immune responses by targeting a specific DC-subset hence enables
full exploitation of the immune system.