Protein Supramolecular Structures: From Self-Assembly to Nanovaccine Design

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.

Harnessing the Activation of Toll-Like Receptor 2/6 by Self-Assembled Cross-β Fibrils to Design Adjuvanted Nanovaccines

“…We evaluated if the M2e epitope is exposed on the fibril surface and not buried inside the hydrophobic core of the nanostructures, which could allow direct recognition by B cells [ 10 , 40 , 41 ]. First, measurement of zeta potential was assessed to evaluate the electrostatic charge on the surface of the M2e-NFs in comparison to naked I 10 fibrils.…”

“…As previously reported [ 25 ], the conjugation of antigenic determinant to fibrillar nanostructures promotes its internalization by APCs, which constitutes a prerequisite for the initiation of the epitope-specific immune response. Moreover, protection of the antigens from proteolytic degradation and depot effect at the immunization site are also likely contributing to the immunostimulatory properties of cross-β fibrils [ 10 , 64 ]. Besides, it remains critical to evaluate if the immunogenicity of amyloid-like fibrils constitutes an intrinsic characteristic of the cross-β quaternary organization, or if different amyloidogenic sequences can lead to divergent immunogenic potency.…”

“…Ideally, nanomaterials used as subunit vaccine platforms need to be biocompatible, biodegradable, to show appropriate physicochemical and enhanced biological stability, and to tolerate the functionalization of a diversity of antigens, from oligosaccharides to large proteins [ 8 , 9 ]. Among materials used for subunit nanovaccines, proteins that self-assemble into well-organized repetitive antigen displays have attracted interest for their high biocompatibility, molecular specificity, and multivalency [ 10 ]. The best-known protein nanovaccines are virus-like particles (VLPs), composed of viral structural proteins that lack nucleic acid sequences [ 11 ], which are currently used as vaccines against the hepatitis B virus and the human papilloma virus [ 12 ].…”

Recent Progress in Nanotechnology for COVID-19 Prevention, Diagnostics and Treatment

“…Lipopolysaccharides are components with diameters of 20–200 nm formed by the self-assembly of viral capsid proteins. These particles have the advantage that they can absolutely mimic the structure and the antigenic epitopes of their similar native viruses because they are free from genetic elements [ 62 ]. Moreover, this repetitive antigen displays effective phagocytosis by APCs following activation.…”

Amyloid-Like Aggregation in Diseases and Biomaterials: Osmosis of Structural Information

“…The remarkable contribution of computational studies in unraveling the structural/dynamic properties of self-assembling systems involved in pathogenic processes has been reviewed elsewhere ( Nasica-Labouze et al, 2015 ). These three-dimensional structural data have been also exploited to design inhibitors of amyloid-like aggregation ( Seidler et al, 2018 ; Griner et al, 2019 ) and nanovaccines ( Luo and Abrahams, 2014 ; Al-Halifa et al, 2020 ; Zottig et al, 2020 ). It is also important to note that solution studies conducted with Small-Angle X-ray Scattering (SAXS) and Small-Angle Neutron Scattering (SANS) techniques have provided a considerable contribution to the characterization of solvent structure and dynamics of cross-β assemblies ( Fichou et al, 2015 ; Langkilde et al, 2015 ; Pounot et al, 2020 ).…”