Lumazine synthase protein cage nanoparticles as antigen delivery nanoplatforms for dendritic cell-based vaccine development

Abstract

PurposeProtein cages are promising nanoplatform candidates for efficient delivery systems due to their homogenous size and structure with high biocompatibility and biodegradability. In this study, we investigate the potential of lumazine synthase protein cage as an antigen delivery system to dendritic cells (DCs), which induce antigen-specific T cell proliferation.Materials and MethodsOvalbumin (OVA) peptides OT-1 (SIINFEKL) and OT-2 (ISQAVHAAHAEINEAGR) were genetically inserted to lumazine synthase and each protein cage was over-expressed in Escherichia coli as a soluble protein. The efficiency of antigen delivery and the resulting antigen-specific T cell proliferation by DCs was examined in vitro as well as in vivo.ResultsWe successfully generated and characterized OVA peptides carrying lumazine synthase protein cages. The OT-1 and OT-2 peptides carried by lumazine synthases were efficiently delivered and processed by DCs in vitro as well as in vivo, and induced proliferation of OT-1-specific CD8+T cells and OT-2-specific CD4+T cells.ConclusionOur data demonstrate the potential of lumazine synthase protein cage being used as a novel antigen delivery system for DC-based vaccine development in future clinical applications.

Immune response to vaccine candidates based on different types of nanoscaffolded RBD domain of the SARS-CoV-2 spike protein

“…1). Even larger number of RBD domains were presented on the icosahedral Aequifex aeolicus lumazine synthase (AaLs), which has also been used before for nanostructured vaccines 60,67 . A short peptide, comprising 24 amino acid residues based on the viral β-annulus protein from tomato bushy stunt virus has been shown to spontaneously form nanoparticles approximately 40 nm in diameter 58 .…”

Nouvelles stratégies d’innovations vaccinales et leurs application en médecine vétérinaire

“…(Plummer & Manchester, 2011). Au-delà des capsides virales, de nombreuses autres protéines naturelles s'auto-assemblent spontanément, la ferritine par exemple étudiée dans des vaccins grippaux, la protéine E2 de Geobacillus stearothermophilus (López-Sagaseta et al 2016), des protéines de synthèse comme 13-01 aldolase (Hsia et al 2016), la lumazine synthase de la bactérie Aquifex aeolicus (Ra et al 2014). Le concept s'élargit de jour en jour avec des microsphères, liposomes, ou micelles naturelles ou synthétiques, des nano-émulsions, des nano-vésicules, des peptides supramoléculaires assemblés en nanofibres, etc… (Wen & Collier, 2015).…”

Protein nanoparticles as multifunctional biocatalysts and health assessment sensors

“…While many PNP systems cannot support direct fusions of large proteins as they can interfere with self-assembly [6,42], many platforms can afford the fusion of small functional peptides [6,8,36,44]. For instance, the tobacco mosaic virus (TMV) nanorod VLP monomers can be modified at the C-terminus with a FLAG tag [44]; however, an “IQ” peptide for Genhance 680 fluorophore binding was found to interfere with the folding and assembly.…”

“…Although most PNPs used today are based on biologically evolved protein assemblies such as viral capsids [5,7] or multimeric enzymes [6,8], there is a move toward engineering these protein nano-assemblies based on in silico design [9,10]. The ability to provide multi-functionalization is often highly challenging as the modifications may result in a loss of nanoparticle self-assembly or protein functionality.…”