The Role of Nanovaccine in Cross-Presentation of Antigen-Presenting Cells for the Activation of CD8+ T Cell Responses

Abstract

Explosive growth in nanotechnology has merged with vaccine development in the battle against diseases caused by bacterial or viral infections and malignant tumors. Due to physicochemical characteristics including size, viscosity, density and electrostatic properties, nanomaterials have been applied to various vaccination strategies. Nanovaccines, as they are called, have been the subject of many studies, including review papers from a material science point of view, although a mode of action based on a biological and immunological understanding has yet to emerge. In this review, we discuss nanovaccines in terms of CD8+ T cell responses, which are essential for antiviral and anticancer therapies. We focus mainly on the role and mechanism, with particular attention to the functional aspects, of nanovaccines in inducing cross-presentation, an unconventional type of antigen-presentation that activates CD8+ T cells upon administration of exogenous antigens, in dendritic cells followed by activation of antigen-specific CD8+ T cell responses. Two major intracellular mechanisms that nanovaccines harness for cross-presentation are described; one is endosomal swelling and rupture, and the other is membrane fusion. Both processes eventually allow exogenous vaccine antigens to be exported from phagosomes to the cytosol followed by loading on major histocompatibility complex class I, triggering clonal expansion of CD8+ T cells. Advancement of nanotechnology with an enhanced understanding of how nanovaccines work will contribute to the design of more effective and safer nanovaccines.

How can nanotechnology help to combat COVID-19? Opportunities and urgent need

“…Furthermore, nanoparticles are able to interact with immune machineries, inducing cellular and humoral immunological responses. Studies have shown that nanoparticles who range in size between 20 and 200 nm are preferentially internalized by endocytosis into APCs (resulting in the T cell response), while large particles (0.5-5 µm) are usually internalized by phagocytosis (inducing the humoral immune response) [178,179].…”

Functional Recognition by CD8+ T Cells of Epitopes with Amino Acid Variations Outside Known MHC Anchor or T Cell Receptor Recognition Residues

“…Hence, the conjugated peptide KI to PSNPs may be internalized by APCs much more efficiently than the same amount of free KI peptides. The peptides conjugated to PSNPs are usually endocytosed and canalize intracellular trafficking toward early endosomal low-degradative compartments rather than lysosomes for degradation [ 30 ]. This favors antigen cross-presentation and consequently enhances CD8+ T cell activation [ 30 ].…”

“…The peptides conjugated to PSNPs are usually endocytosed and canalize intracellular trafficking toward early endosomal low-degradative compartments rather than lysosomes for degradation [ 30 ]. This favors antigen cross-presentation and consequently enhances CD8+ T cell activation [ 30 ]. Therefore, conjugation of peptide KI to PSNPs would increase DC uptake as well as antigen processing and presentation on MHC class I molecules.…”

COVID-19 infection and nanomedicine applications for development of vaccines and therapeutics: An overview and future perspectives based on polymersomes

“…One of the important approaches in protection against viral infections is that of targeting the T cell-mediated immune response. Studies have shown that nanovaccines have the potential for cross-presentation of antigens to cytotoxic T cells ( Kim et al, 2019 ). Therefore, nanomaterials such as self-assembled nanostructures, liposomes, nanocrystals, dendrimers, nanosuspensions, nanoemulsions, polymeric nanostructures, micelles and nanoparticles comprising lipids, carbohydrates or other organic molecules may emerge as promising tools in fighting COVID-19 ( Lembo et al, 2018 ; Six and Ferji, 2019 ), especially in terms of enhancing vaccine development and therapeutic efficiency of the repurposed or novel antiviral drugs.…”