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.
Highlights
Nanotechnology has been applied to various fields of medical research including vaccine development
Considering that most vaccines are administrated as exogenous antigen, cross-presentation can play a major role in the initiation of CD8+ T cell responses especially against cancers and other infectious diseases caused by intracellular pathogens [5,8]
Application of nanotechnology to vaccinology has succeeded in enhancing the effectiveness of vaccines, and the introduction of nanovaccines has produced a new paradigm for vaccine development
Summary
Nanotechnology has been applied to various fields of medical research including vaccine development. The advantages of nanosized particles (NPs), including upregulation of immune response, safety with biodegradability, tissue or cell target ability through size modulation, and conjugation with immune-regulatory factors, can be utilized at several stages of vaccine development. As most vaccines used in the field are exogenous to the cell, DCs have a critical role in vaccine inducing activation of cytotoxic T lymphocyte (CTL) responses against viral or cancerous diseases For this reason, various strategies for nanovaccines have been designed to target DCs [2,9]. By addressing the key concept of how nanovaccines activate CD8+ T cell responses, we discuss (1) how nanoparticles advance antigenicity and adjuvanticity to enhance effectiveness, (2) nanovaccines which target lymph nodes (LNs) and APCs, and (3) intracellular mechanism to harness cross-presentation of DCs. 2. Nanoparticles Incorporated with Antigens and Adjuvants for CD8+ T Cell Response
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