CpG-induced inflammatory DCs promote strong Th1/CTL responses to particulate antigens (52.11)

Abstract

Abstract Increasing safety issues are now driving the vaccine field to develop vaccines composed of recombinant antigens. Most protein antigens are however poorly immunogenic and require the addition of immunepotentiators to evoke immunity. Moreover, compared to particulate antigens, uptake and presentation of soluble antigens by DCs is far inferior. By encapsulating antigens into polyelectrolyte-based particles modified with TLR ligands, we aim to create entirely synthetic but non-pathological mimics of micro-organisms. Encapsulating OVA in these particles strongly increased antigen presentation by DCs via MHCI and MHCII. Although antigen encapsulation in these particles was sufficient to elicit immunity, the strength of the induced Th1 and CTL response was dramatically increased by functionalizing the particles with the TLR9 ligand CpG, yielding protective immunity against B16-OVA melanoma. Importantly, the particulate formulation was also far superior to a mixture of soluble antigen and CpG. Injection of CpG resulted in a strong recruitment of monocyte-derived inflammatory DCs in the draining lymph nodes, which were totally absent in CCR2-/- mice. Although immune responses to soluble antigen and CpG remained unaffected in CCR2-/- mice, the strong Th1/CTL response observed in wild type mice to particulate antigen/CpG was almost totally abrogated in the CCR2-/- mice, pinpointing to important differences in how T-cell responses are initiated to particulate and soluble antigens.