Abstract
Life-inspired protein supramolecular assemblies have recently attracted considerable attention for the development of next-generation vaccines to fight against infectious diseases, as well as autoimmune diseases and cancer. Protein self-assembly enables atomic scale precision over the final architecture, with a remarkable diversity of structures and functionalities. Self-assembling protein nanovaccines are associated with numerous advantages, including biocompatibility, stability, molecular specificity and multivalency. Owing to their nanoscale size, proteinaceous nature, symmetrical organization and repetitive antigen display, protein assemblies closely mimic most invading pathogens, serving as danger signals for the immune system. Elucidating how the structural and physicochemical properties of the assemblies modulate the potency and the polarization of the immune responses is critical for bottom-up design of vaccines. In this context, this review briefly covers the fundamentals of supramolecular interactions involved in protein self-assembly and presents the strategies to design and functionalize these assemblies. Examples of advanced nanovaccines are presented, and properties of protein supramolecular structures enabling modulation of the immune responses are discussed. Combining the understanding of the self-assembly process at the molecular level with knowledge regarding the activation of the innate and adaptive immune responses will support the design of safe and effective nanovaccines.
Highlights
Vaccination has constituted the strategy of choice to prevent the propagation infectious diseases and has shown tremendous potential for treatment of cancer and autoimmune diseases [1,2]
The continuous emergence of novel pathogens and the fact that no vaccines exist for numerous ongoing infectious diseases reinforce the importance of developing safe, scalable, efficient and affordable vaccination technologies
Subunit vaccines represent an alternative strategy to vaccine formulations based on live-attenuated and inactivated whole pathogens, they suffer from weak immunogenicity and necessitate the addition of adjuvants
Summary
Vaccination has constituted the strategy of choice to prevent the propagation infectious diseases and has shown tremendous potential for treatment of cancer and autoimmune diseases [1,2]. An alternative strategy to increase the immunogenicity of subunit vaccines consists of developing nanoparticles exposing a high density of the relevant antigens These nanovaccines combine numerous advantages, including improved immunogenicity, increased uptake by antigen-presenting cells (APCs) and stabilization of the antigen [7]. Synthetic and inorganic nanoparticles, such as polymers and gold nanoparticles, were evaluated to enhance antigen processing and/or as non-specific immunostimulants [8] These nanoparticles present limitations associated with their toxicity, low stability and/or poor biocompatibility. Subunit nanovaccines composed of proteins that self-assemble into well-organized repetitive antigen display platforms have recently attracted interest for their unique properties, such as biocompatibility, enhanced stability, molecular specificity and multivalency, leading to efficient delivery and presentation of antigenic determinants [9]. We highlight some of the recent and elegant works on nanovaccine design and discuss the structural and physicochemical properties of the protein assemblies that modulate the potency and the polarization of the immune responses
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