Spike Ferritin Nanoparticle Covid-19 vaccine

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The US Army has recently developed a SARS-CoV-2 sub-unit vaccine based on a ferritin nanoparticle platform that displays a pre-fusion stabilized spike on its surface [1]. The spike protein was modified to generate a stable spike trimer formation on the ferritin molecule. The stabilized prefusion-spike protein of the Wuhan-Hu-1 strain of SARS-CoV-2 was genetically linked to form a ferritin-fusion recombinant protein, which naturally forms a Spike Ferritin nanoparticle (SpFN). Ferritin is a naturally occurring, ubiquitous, iron-carrying protein that self-oligomerizes into a 24-unit spherical particle and is currently being evaluated as a vaccine platform for influenza in two phase 1 clinical trials (NCT03186781, NCT03814720) with two further trials in the recruitment phase for Epstein-Barr virus (NCT04645147) and Influenza H10 (NCT04579250).

Walter Reed Army Institute of Research (WRAIR) reported on a series of recently published preclinical study results showing that the Spike Ferritin Nanoparticle (SpFN) COVID-19 vaccine not only elicits a potent immune response but may also provide broad protection against SARS-CoV-2 variants of concern as well as other coronaviruses. The report says: “This vaccine stands out in the COVID-19 vaccine landscape. The repetitive and ordered display of the coronavirus spike protein on a multi-faced nanoparticle may stimulate immunity in such a way as to translate into significantly broader protection.”

Scientists in WRAIR’s Emerging Infectious Diseases Branch (EIDB) developed the SpFN nanoparticle vaccine, based on a ferritin platform, as part of a forward-thinking “pan-SARS” strategy that aims to address the current pandemic and acts as a first line of defense against variants of concern and similar viruses that could emerge in the future.

Compared with other nanocarriers such as liposomes, mesoporous silica, and cyclodextrin, ferritin as a typical protein nanocage has received considerable attention in the field of food, nutrition, and medicine owing to its inherent cavity size, excellent water solubility, and biocompatibility [2]. Additionally, ferritin nanocage also serves as a versatile bio-template for the synthesis of a variety of nanoparticles. Recently, scientists have explored the ferritin nanocage structure for encapsulation and delivery of guest molecules such as nutrients, bioactive molecules, anticancer drugs, and mineral metal ions by taking advantage of its unique reversible disassembly and reassembly property and biomineralization.

(A) Structure of ferritin and its outer/inter diameter. (B) Graphic representation of ferritin subunit structure. (C) The inter-subunit interfaces of ferritin and the pore size at two different interfaces. [2]

[1] Carmen, J.M., Shrivastava, S., Lu, Z. et al. SARS-CoV-2 ferritin nanoparticle vaccine induces robust innate immune activity driving polyfunctional spike-specific T cell responses. npj Vaccines 6, 151 (2021). https://doi.org/10.1038/s41541-021-00414-4

[2] Zhang C, Zhang X, Zhao G. Ferritin Nanocage: A Versatile Nanocarrier Utilized in the Field of Food, Nutrition, and Medicine. Nanomaterials (Basel). 10(9):1894 (2020).doi:10.3390/nano10091894

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