Abstract
A major challenge for vaccine development is targeting antigens to dendritic cells (DCs) in vivo, enabling cross-presentation, and inducing the memory responses. Fcγ receptors (FcγRs) are expressed on many cell types including DCs. Therefore, targeting of antigen to DCs via FcγRs is an attractive strategy for vaccine development. This study employ formyl peptide receptor-like 1 inhibitory protein (FLIPr), an FcγR binding protein secreted by Staphylococcus aureus, to deliver antigen to DCs. Our results show that FLIPr is a competent vehicle in delivering antigen to CD8+ DCs for induction of potent immunities without extra adjuvant formulation. Fusion antigen with FLIPr enables effective antigen presentation on both MHC class II and class I to induce memory T cell responses. Altogether, using FLIPr as an antigen delivery vector has great potential to apply antigens for cancer immunotherapy as well as other infectious disease vaccines.
Highlights
Antigen-presenting cells (APCs) are critical in the induction of immune responses
There was no interaction between recombinant OVA (rOVA) and different Fcγ receptors (FcγRs) isoforms we tested. These results indicate that rOVA-formyl peptide receptor-like inhibitory protein (FLIPr) possesses the ability of binding to different FcγR isoforms
There were no significant differences in CD40 and MCH class II relative mean fluorescence intensity (MFI) of plasmacytoid DCs (pDCs) among PBS, rOVA, and rOVA-FLIPr injection groups (Figure 7B, lower panel). These results indicate that injection of rOVA-FLIPr elevate CD40 and MCH class II expression of CD8+ Dendritic cells (DCs) but not CD8− DCs, and pDCs
Summary
Antigen-presenting cells (APCs) are critical in the induction of immune responses. Professional APCs capture and process antigens in the peripheral tissue, express lymphocyte co-stimulatory molecules, migrate to lymphoid organs, secrete cytokines to initiate immune responses. Dendritic cells (DCs) are the most potent APCs. Dendritic cells (DCs) are the most potent APCs They play a critical role during the initiation of adaptive immune responses, which inducing differentiation of naïve T cells (CD4+ or CD8+ T cells) into effector cells (helper or cytotoxic T cells) and further regulation of humoral immune responses [1,2,3]. Several reports have shown that antibody-bound soluble antigens facilitate DCs to activate antigen-specific T cells more efficiently than free antigens [8,9,10,11,12,13] These results support that FcγRs play an important role in augmenting antigen presentation.
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