Aryan Rezvani

Introduction: Since its emergence in Wuhan, China, SARS-CoV-2 has remained a massive public health challenge.¹ Efforts to actively immunize the population through vaccination have increased over the past few months. However, studies performed early in the pandemic demonstrated a poorly sustained humoral response following infection.² Therefore, the duration of vaccine-induced protective immunity has also been of concern. The goal of our literature review was two-fold. First, we aimed to discuss the application of ferritin nanoparticles in vaccine development briefly. Second, we sought to evaluate the use of ferritin nanoparticle-based receptor-binding domain vaccines (ferritin NP-RBD vaccines) in producing long-lasting protective immunity against SARS-CoV-2. Methods: An electronic literature search was performed using PubMed, with the following search terms and filtered for articles published in 2020 and 2021: «ferritin nanoparticle SARS-CoV-2» and «ferritin nanomaterial SARS-CoV-2». Sixteen and ten results for each respective search criterion were obtained and screened in two phases by the author. The first phase involved reading the title and abstract, and the second, the entirety of each paper. The author identified five articles for qualitative synthesis. Results: Ferritin NP-RBD vaccines produce robust antibody responses in mammalian models.^2-4 The duration of this response has been demonstrated to be as long as seven months in mice.² Combined intramuscular and intranasal administration improves viral clearance in ferrets.⁵ Mice and rhesus macaques vaccinated with Ferritin NP-RBD or RBD-heptad repeat vaccines show robust CD8⁺ T-cell and Th1-favouring CD4⁺ T-cell responses.⁴ As for optimizing ferritin nanocage constructs, a five amino acid-based short linker may be the best option (compared to no-linker or 13-amino acid-based long linker) to improve ACE2 receptor binding.⁶  Conclusion: Studies indicate that ferritin NP-RBD vaccines are equally or even more immunogenic than their RBD protein subunit counterparts.^2-4 Notably, the inoculation method of ferritin NP-RBD vaccines may improve said immunogenicity.⁵ The antibody response might also be long-lasting,² but the literature on this topic remains limited. From an engineering standpoint, adjusting parameters like synthetic linkers alters ferritin-RBD interactions and may be a point of leverage in vaccine development.⁶ Conclusively, ferritin NP-RBD vaccines appear to be a good candidate for vaccine development, eliciting powerful B-cell and T-cell responses. However, the number of studies remains few, and therefore, more investigations are needed.

1. Baviskar T, Raut D, Bhatt LK. Deciphering Vaccines for COVID-19: where do we stand today? Immunopharmacol Immunotoxicol. Feb 2021;43(1):8-21. doi:10.1080/08923973.2020.1837867
2. Wang W, Huang B, Zhu Y, Tan W, Zhu M. Ferritin nanoparticle-based SARS-CoV-2 RBD vaccine induces a persistent antibody response and long-term memory in mice. Cell Mol Immunol. 03 2021;18(3):749-751. doi:10.1038/s41423-021-00643-6
3. Kang YF, Sun C, Zhuang Z, et al. Rapid Development of SARS-CoV-2 Spike Protein Receptor-Binding Domain Self-Assembled Nanoparticle Vaccine Candidates. ACS Nano. 02 2021;15(2):2738-2752. doi:10.1021/acsnano.0c08379
4. Ma X, Zou F, Yu F, et al. Nanoparticle Vaccines Based on the Receptor Binding Domain (RBD) and Heptad Repeat (HR) of SARS-CoV-2 Elicit Robust Protective Immune Responses. Immunity. 12 2020;53(6):1315-1330.e9. doi:10.1016/j.immuni.2020.11.015
5. Kim YI, Kim D, Yu KM, et al. Development of Spike Receptor-Binding Domain Nanoparticles as a Vaccine Candidate against SARS-CoV-2 Infection in Ferrets. mBio. 03 2021;12(2)doi:10.1128/mBio.00230-21
6. Kalathiya U, Padariya M, Fahraeus R, Chakraborti S, Hupp TR. Multivalent Display of SARS-CoV-2 Spike (RBD Domain) of COVID-19 to Nanomaterial, Protein Ferritin Nanocages. Biomolecules. 02 2021;11(2)doi:10.3390/biom11020297