Adjuvants Enhancing Cross-Presentation by Dendritic Cells: The Key to More Effective Vaccines?

Nataschja I Ho,Lisa G M Huis In 'T Veld,Tonke K Raaijmakers,Gosse J Adema

doi:10.3389/fimmu.2018.02874

Abstract

Over the last decades, vaccine development has advanced significantly in pursuing higher safety with less side effects. However, this is often accompanied by a reduction in vaccine immunogenicity and an increased dependency on adjuvants to enhance vaccine potency. Especially for diseases like cancer, it is important that therapeutic vaccines contain adjuvants that promote strong T cell responses. An important mode of action for such adjuvants is to prolong antigen exposure to dendritic cells (DCs) and to induce their maturation. These mature DCs are extremely effective in the activation of antigen-specific T cells, which is a pre-requisite for induction of potent and long-lasting cellular immunity. For the activation of CD8+ cytotoxic T cell responses, however, the exogenous vaccine antigens need to gain access to the endogenous MHCI presentation pathway of DCs, a process referred to as antigen cross-presentation. In this review, we will focus on recent insights in clinically relevant vaccine adjuvants that impact DC cross-presentation efficiency, including aluminum-based nanoparticles, saponin-based adjuvants, and Toll-like receptor ligands. Furthermore, we will discuss the importance of adjuvant combinations and highlight new developments in cancer vaccines. Understanding the mode of action of adjuvants in general and on antigen cross-presentation in DCs in particular will be important for the design of novel adjuvants as part of vaccines able to induce strong cellular immunity.

Highlights

Since the development of the first successful vaccine by Edward Jenner in 1796 against smallpox, a lot of research has been done on the development of vaccines against other diseases
For the development of new vaccines many aspects should be taken into consideration such as the nature of the antigenic material, the type of immune memory responses that needs to be induced, and the administration and delivery routes, which might reduce the risk of side effects
An important characteristic of adjuvants able to induce cellular immunity is the efficient delivery of the target antigen into professional antigen presenting dendritic cells (DCs) and its potency in activating these DCs

Summary

INTRODUCTION

Since the development of the first successful vaccine by Edward Jenner in 1796 against smallpox, a lot of research has been done on the development of vaccines against other diseases. An important characteristic of adjuvants able to induce cellular immunity is the efficient delivery of the target antigen into professional antigen presenting dendritic cells (DCs) and its potency in activating these DCs. In general, DC maturation enhances their antigen presentation capacity and ability to activate T cells and is a prerequisite for induction of potent and long-lasting immunity. A very important characteristic of adjuvants that has received much less attention is their ability to induce presentation of exogenous antigens in MHCII to CD4+ T cells and in MHCI to CD8+ T cells. It has been reported that cross-presentation is important for inducing T cell responses specific for tumor antigens and infectious diseases [26,27,28]. In the vacuolar pathway antigens are degraded by proteases in endo/lysosomal compartments and directly loaded on MHCI

Lipid vesicle containing inactivated viral proteins

Malaria Pandemic influenza

TLR Ligands

FUTURE PERSPECTIVES