A Lipid Based Antigen Delivery System Efficiently Facilitates MHC Class-I Antigen Presentation in Dendritic Cells to Stimulate CD8+ T Cells

Mithun Maji,Saumyabrata Mazumder,Nahid Ali,Souparno Bhattacharya,Abdus Sabur,Md Shadab,Pradyot Bhattacharya,Somsubhra Thakur Choudhury

doi:10.1038/srep27206

Abstract

The most effective strategy for protection against intracellular infections such as Leishmania is vaccination with live parasites. Use of recombinant proteins avoids the risks associated with live vaccines. However, due to low immunogenicity, they fail to trigger T cell responses particularly of CD8+ cells requisite for persistent immunity. Previously we showed the importance of protein entrapment in cationic liposomes and MPL as adjuvant for elicitation of CD4+ and CD8+ T cell responses for long-term protection. In this study we investigated the role of cationic liposomes on maturation and antigen presentation capacity of dendritic cells (DCs). We observed that cationic liposomes were taken up very efficiently by DCs and transported to different cellular sites. DCs activated with liposomal rgp63 led to efficient presentation of antigen to specific CD4+ and CD8+ T cells. Furthermore, lymphoid CD8+ T cells from liposomal rgp63 immunized mice demonstrated better proliferative ability when co-cultured ex vivo with stimulated DCs. Addition of MPL to vaccine enhanced the antigen presentation by DCs and induced more efficient antigen specific CD8+ T cell responses when compared to free and liposomal antigen. These liposomal formulations presented to CD8+ T cells through TAP-dependent MHC-I pathway offer new possibilities for a safe subunit vaccine.

Highlights

Promising as delivery vehicles owing to their low immunogenicity, safety in clinical use, depot effect and simplicity of preparation[20,21,22]
We report that Distearoyl phosphatidylcholine (DSPC) bearing cationic liposomes were efficiently taken up by bone-marrow derived dendritic cells (BMDCs), and transported to different intracellular compartments
On the basis of the capacity to upregulate the expression of surface co-stimulatory molecules, as well as to promote the IL-12p40 and nitric oxide (NO) production in DCs, it can be concluded that positively charged liposomes activate and promote the maturation of DCs efficiently

Summary

Introduction

Promising as delivery vehicles owing to their low immunogenicity, safety in clinical use, depot effect and simplicity of preparation[20,21,22] These liposomes are very efficiently taken up by APCs23. Addition of positively charged moieties improves both entrapment as well as retaining efficiency of biological macromolecules along with enhancing uptake by APCs12,23,27 This allows persistence of antigens for durable uptake and presentation needed for long term immunity for diseases like leishmaniasis[28,29]. Decrease in CD8+ T cell proliferation in TAP1 silenced DCs suggests that liposomal antigens are presented through a TAP-dependent MHC-I pathway These results, demonstrate the potentiality of this formulation as a promising antigen delivery technology for stimulation of T cell responses

Methods

Results

Conclusion