Functionalizing Ferritin Nanoparticles for Vaccine Development

Abstract

In the last decade, the interest in ferritin-based vaccines has been increasing due to their safety and immunogenicity. Candidates against a wide range of pathogens are now on Phase I clinical trials namely for influenza, Epstein-Barr, and SARS-CoV-2 viruses. Manufacturing challenges related to particle heterogeneity, improper folding of fused antigens, and antigen interference with intersubunit interactions still need to be overcome. In addition, protocols need to be standardized so that the production bioprocess becomes reproducible, allowing ferritin-based therapeutics to become readily available. In this review, the building blocks that enable the formulation of ferritin-based vaccines at an experimental stage, including design, production, and purification are presented. Novel bioengineering strategies of functionalizing ferritin nanoparticles based on modular assembly, allowing the challenges associated with genetic fusion to be circumvented, are discussed. Distinct up/down-stream approaches to produce ferritin-based vaccines and their impact on production yield and vaccine efficacy are compared. Finally, ferritin nanoparticles currently used in vaccine development and clinical trials are summarized.

Induction of Broadly Cross-Reactive Antibody Responses to SARS-CoV-2 Variants by S1 Nanoparticle Vaccines

“…Finally, the I53-50 NP was coassembled from 20 trimeric I53-50A and 12 pentameric I53-50B subunits to form an icosahedral nanoparticle ( 48 , 49 ). These three nanoparticles were found to be safe, stable, and easy to produce in previous studies ( 32 , 50 – 52 ).…”

Virus-Like Particles: Revolutionary Platforms for Developing Vaccines Against Emerging Infectious Diseases

“…Self-assembly can be achieved in such circumstances by attaching these antigens to an oligomeric protein platform ( Nguyen and Tolia, 2021 ). There are many naturally occurring oligomeric proteins such as lumazine synthase (LS) ( Ladenstein and Morgunova, 2020 ), ferritin ( Rodrigues et al, 2021 ), dihydrolipoyl acetyltransferase (E2p) ( He et al, 2016 ), non-structural protein 10 (nsp10) ( Carter et al, 2020 ), encapsulin ( Lagoutte et al, 2018 ), and heat shock proteins (HSPs) ( Richert et al, 2012 ) that have been developed for platform design for designing targeted therapeutics. The display of viral glycoproteins using NPs is effective in developing antigen-specific antibodies ( Ueda et al, 2020 ).…”

“…Among the wide array of platforms available for the display of antigens, ferritin has emerged as a major protein complex that can be combined with NPs for vaccine development ( Diaz-Arévalo and Zeng, 2020 ). Due to its high pH and thermal stability, it allows for easy annealability with surface molecules ( Rodrigues et al, 2021 ). In recent years, ferritin has been studied in preclinical studies as a viable vaccine platform for numerous viral infectious diseases, including HIV, H1N1, HCV, HBV, HFMD, Epstein–Barr, rotavirus, and respiratory diseases caused by coronaviruses ( Butkovich et al, 2021 ).…”

Cyclosporine A loaded brain targeting nanoparticle to treat cerebral ischemia/reperfusion injury in mice

“…The cage structure is usually composed of heavy chain ferritin (HFn, 21 kDa) subunits and light chain ferritin (LFn, 19 kDa) subunits. As a drug carrier, HFn does not cause toxicity and immune rejection reaction in human body [ 21 ]. In addition, HFn has unique self-assembly properties to form nanoparticle [ 22 ].…”