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Second career of a biosynthetic enzyme: Lumazine synthase as a virus-like nanoparticle in vaccine development.

ABSTRACT: Naturally occurring and computationally ab initio designed protein cages can now be considered as extremely suitable materials for new developments in nanotechnology. Via self-assembly from single identical or non-identical protomers large oligomeric particles can be formed. Virus-like particles have today found a number of quite successful applications in the development of new vaccines. Complex chimeric nanoparticles can serve as suitable platforms for the presentation of natural or designed antigens to the immune system of the host. The scaffolds can be cage forming highly symmetric biological macromolecules like lumazine synthase or symmetric self-assembling virus-like particles generated by computational ab initio design. Symmetric nanoparticle carriers display a structurally ordered array of immunogens. This feature can lead to a more favorable interaction with B-cell receptors, in comparison to the administration of single recombinant immunogens. Several pre-clinical animal studies and clinical studies have recently pointed out the efficiency of nanoparticle antigens produced recombinantly in creating strong immune responses against infectious diseases like HIV, Malaria, Borrelia, Influenza.

SUBMITTER: Ladenstein R

PROVIDER: S-EPMC7369331 | biostudies-literature | 2020 Sep

REPOSITORIES: biostudies-literature

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Second career of a biosynthetic enzyme: Lumazine synthase as a virus-like nanoparticle in vaccine development.

Ladenstein Rudolf R Morgunova Ekaterina E

Biotechnology reports (Amsterdam, Netherlands) 20200706

Naturally occurring and computationally <i>ab initio</i> designed protein cages can now be considered as extremely suitable materials for new developments in nanotechnology. Via self-assembly from single identical or non-identical protomers large oligomeric particles can be formed. Virus-like particles have today found a number of quite successful applications in the development of new vaccines. Complex chimeric nanoparticles can serve as suitable platforms for the presentation of natural or des ...[more]

PMID: 32714852

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Project description:Influenza is an infectious respiratory illness caused by influenza viruses. Despite yearly updates, the efficacy of influenza vaccines is significantly curtailed by the virus antigenic drift and antigenic shift. These constant changes to the influenza virus make-up also challenge the development of a universal flu vaccine, which requires conserved antigenic regions shared by influenza viruses of different subtypes. We propose that it is possible to bypass these challenges by the development of an influenza vaccine based on conserved proteins delivered in an adjuvanted nanoparticle system. In this study, we generated influenza nanoparticle constructs using trimethyl chitosan nanoparticles (TMC nPs) as the carrier of recombinant influenza hemagglutinin subunit 2 (HA2) and nucleoprotein (NP). The purified HA2 and NP recombinant proteins were encapsulated into TMC nPs to form HA2-TMC nPs and NP-TMC nPs, respectively. Primary human intranasal epithelium cells (HNEpCs) were used as an in vitro model to measure immunity responses. HA2-TMC nPs, NP-TMC nPs, and HA2-NP-TMC nPs (influenza nanoparticle constructs) showed no toxicity in HNEpCs. The loading efficiency of HA2 and NP into the TMC nPs was 97.9% and 98.5%, respectively. HA2-TMC nPs and NP-TMC nPs more efficiently delivered HA2 and NP proteins to HNEpCs than soluble HA2 and NP proteins alone. The induction of various cytokines and chemokines was more evident in influenza nanoparticle construct-treated HNEpCs than in soluble protein-treated HNEpCs. In addition, soluble factors secreted by influenza nanoparticle construct-treated HNEpCs significantly induced MoDCs maturation markers (CD80, CD83, CD86 and HLA-DR), as compared to soluble factors secreted by protein-treated HNEpCs. HNEpCs treated with the influenza nanoparticle constructs significantly reduced influenza virus replication in an in vitro challenge assay. The results indicate that TMC nPs can be used as influenza vaccine adjuvants and carriers capable of delivering HA2 and NP proteins to HNEpCs.

Dataset Information

Second career of a biosynthetic enzyme: Lumazine synthase as a virus-like nanoparticle in vaccine development.

Publications

Second career of a biosynthetic enzyme: Lumazine synthase as a virus-like nanoparticle in vaccine development.

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