Biodegradable Polymeric Nanoparticles-Based Vaccine Adjuvants for Lymph Nodes Targeting

Abstract

Vaccines have successfully eradicated a large number of diseases. However, some infectious diseases (such as HIV, Chlamydia trachomatis or Bacillus anthracis) keep spreading since there is no vaccine to prevent them. One way to overcome this issue is the development of new adjuvant formulations which are able to induce the appropriate immune response without sacrificing safety. Lymph nodes are the site of lymphocyte priming by antigen-presenting cells and subsequent adaptive immune response, and are a promising target for vaccine formulations. In this review, we describe the properties of different polymer-based (e.g., poly lactic-co-glycolic acid, poly lactic acid …) particulate adjuvants as innovative systems, capable of co-delivering immunopotentiators and antigens. We point out how these nanoparticles enhance the delivery of antigens, and how their physicochemical properties modify their uptake by antigen-presenting cells and their migration into lymph nodes. We describe why polymeric nanoparticles increase the persistence into lymph nodes and promote a mature immune response. We also emphasize how nanodelivery directs the response to a specific antigen and allows the induction of a cytotoxic immune response, essential for the fight against intracellular pathogens or cancer. Finally, we highlight the interest of the association between polymer-based vaccines and immunopotentiators, which can potentiate the effect of the molecule by directing it to the appropriate compartment and reducing its toxicity.

Keywords: adjuvant; antigen; immunogenicity; lymph node; molecular adjuvant; nanodelivery; nanoparticles; polymer; vaccine.

Figure 1

Pathways of endocytosis of exogenous particles, molecules or pathogens. According to the size of an extracellular molecule or particle, different endocytosis pathways take place to engulf it into the cell. Particles between 50 and 80 nm are taken into the cell through caveolin-mediated endocytosis, <150 nm by clathrin-mediated endocytosis, 0.5 to 5 µm through macropinocytosis and larger than 0.5 µm through phagocytosis.

Figure 2

From vaccine administration to immune response. Administered NPs are firstly uptaken by APCs and the antigen is processed to be presented by the appropriate MHC. Antigenic peptide presented through MHC-I induce cytotoxic immune response, the peptides presented through MHC-II can activate CD4⁺ T cells that can provide help for the humoral immune response.