Enhanced delivery of Mycobacterium tuberculosis antigens to antigen presenting cells using RVG peptide

Abstract

Among the various strategies to improve vaccines against infectious diseases, targeting of antigens to dendritic cells (DCs), which are professional antigen presenting cells (APCs), has received increased attention in recent years. Here, we investigated whether a synthetic peptide region named RVG, originated from Rabies Virus Glycoprotein that binds to the α-7 subunit of the nicotinic acetylcholine receptors (AchR-α7) of APCs, could be used for the delivery of Mycobacterium tuberculosis (Mtb) peptide antigens to DCs and macrophages. Mouse bone marrow derived DCs (BMDCs) and human THP-1 macrophages stimulated with RVG fused peptide epitopes 85B₂₄₁ and 85B₉₆ (represent Ag85B_241-256 and Ag85B_96-111, respectively) from antigen 85B (Ag85B) of Mtb showed enhanced antigen presentation as compared to unfused peptide epitopes and BCG. Further, BMDCs stimulated with RVG fused 85B₂₄₁ showed higher levels of IL-12 positive cells. Consistent with in vitro data, splenocytes of mice immunized with RVG-85B₂₄₁ showed increased number of antigen specific IFN-γ, IL-2, and TNF-α producing cells in relation to splenocytes from mice immunized with 85B₂₄₁ alone. These results suggest that RVG may be a promising tool to develop effective alternate vaccines against tuberculosis (TB).

Keywords: Antigen; Delivery; Dendritic cells; Macrophages; Mice; RVG; Tuberculosis; Vaccine.