Self-assembling SARS-CoV-2 spike protein-directed nanoparticle vaccines

A recent study posted to the Research Square* preprint server depicted the generation of self-assembling coronavirus disease 2019 (COVID-19) nanoparticle vaccines.

Study: Self-assembling SARS-CoV-2 nanoparticle vaccines targeting the S protein induces protective immunity in mice. Image Credit: PhotobyTawat/Shutterstock


The deployment of adequate physical protective measures and the expenditure of large quantities of health and medical resources are required to combat the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Simultaneously, establishing an effective COVID-19 vaccination strategy is critical for curbing the ongoing SARS-CoV-2 pandemic.

The SARS-CoV-2 homotrimer glycoprotein called spike (S) is the most vital antigen target in COVID-19 vaccine development and research. The most probable option to enhance the immune protective impact of the SARS-CoV-2 vaccine is by the complete simulation of the advanced S protein structure in the subunit vaccine development technique.

About the study

In the present study, the scientists adopted a self-assembly technique of the Helicobacter pylori ferritin nanoparticle for preparing the SARS-CoV-2 S protein S1 region, ectodomain (ECD), and receptor-binding domain (RBD) trimer nano-vaccines. For this, the team employed the Bombyx mori nuclear polyhedrosis virus (BmNPV) baculovirus expression system (BES), named reBmBac. This led to the fusion expression of ECD, S1 subunit, and RBD sequences with Helicobacter pylori ferritin, respectively. 

Western blot analysis was performed to detect the expression of fusion proteins generated during the study in silkworms. Immunoelectron microscopy (IEM) and transmission electron microscopy (TEM) were used to analyze the self-assembling ability of the three nanoparticles: S1-Nano, RBD-Nano, and ECD-Nano. 

Immunogenicity of the three nanoparticles via oral and subcutaneous routes was estimated in BALB/c mice by vaccinating them twice with a three-week gap. The doses assessed were 50μg of the ECD-Nano or equivalent moles of RBD-Nano and S1-Nano for the oral route and 10μg of ECD-Nano or comparable moles of RBD-Nano and S1-Nano for the subcutaneous route in mice. The safety of oral vaccination with the three COVID-19 nano-vaccines was determined through high-dose investigations in mice.


The study results illustrated that the three SARS-CoV-2 nanoparticle vaccines developed comprising S1 region, ECD, and RBD trimers with Helicobacter pylori ferritin, respectively, had significant levels of fusion protein expression and self-assembled to 24-mer nanoparticles in the silkworms. All three COVID-19 nanoparticle vaccines generated protective immunity in mice against SARS-CoV-2 through subcutaneous and oral delivery routes. The researchers found that the SARS-CoV-2 nano-vaccines might be utilized to establish efficient immunization programs in underdeveloped regions due to the stability of ferritin nanoparticles.

Breaking SARS-CoV-2 transmission chains in animals, primarily farm and pet animals, was critical in COVID-19 management. The investigators demonstrated that animal vaccinations against SARS-CoV-2 could be generated using the ferritin nanoparticle-based technology, similar to the development of animal vaccines for influenza and rabies. 

The authors demonstrated a preliminary-level confirmation of the efficiency of the SARS-CoV-2 S1 subunit, RBD, and ECD trimer nanoparticle vaccines from their neutralizing antibody and specific antibody titers in mice. Antibodies in mice vaccinated with ECD-Nano, S1-Nano, and RBD-Nano hindered the SARS-CoV-2 RBD-human angiotensin-converting enzyme 2 (hACE2) receptor interaction. In a titer of 1:32 and 1:48, S1-Nano and ECD-Nano hampered the SARS-CoV-2 Delta infection, respectively.

Among the three vaccines evaluated, the ECD-trimer nano-vaccine exhibited a substantial degree of neutralizing antibody titer against SARS-CoV-2, indicating that it was a putative candidate for further development as a COVID-19 nano-vaccine. The higher efficacy of the COVID-19 ECD-Nano vaccines might be due to the presence of both S1 and S2 extracellular regions in them.

The behavior and body temperature of the mice were normal following high-dose and continuous oral vaccinations with the RBD-Nano, ECD-Nano, and S1-Nano. Moreover, no histopathological alterations in any organs or pathological characterization were observed in the three vaccine groups. Notably, the antibody titer in the oral immunization group was higher than in the injection cohort.


The study findings showed that the three COVID-19 vaccines based on SARS-CoV-2 RBD, ECD, and S1 developed in this research, which utilized the ferritin nanoparticle-based strategy, induced antiviral immune responses via both the oral and subcutaneous administration routes.

The presently developed ferritin-based COVID-19 nanoparticle vaccines might offer a low-cost and easy-to-use oral vaccination approach that can compensate for vaccination blind spots generated by a lack of medical resources and ultra-low-temperature devices in underdeveloped regions. This could be possible due to the stability of the ferritin-based SARS-CoV-2 nanoparticle vaccines.

Furthermore, the researchers stated that COVID-19 oral vaccination was a powerful technique for halting SARS-CoV-2 transmission in farmed and domestic animals, particularly wild and stray animals.

*Important notice

Research Square publish preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
  • Xingjian Liu, Haozhi Song, Jianmin Jiang et al. (2022).Self-assembling SARS-CoV-2 nanoparticle vaccines targeting the S protein induce protective immunity in mice. Research Squaredoi:

Posted in: Medical Science News | Disease/Infection News

Tags: Angiotensin, Angiotensin-Converting Enzyme 2, Antibodies, Antibody, Antigen, Coronavirus, Coronavirus Disease COVID-19, covid-19, Efficacy, Electron, Electron Microscopy, Enzyme, Glycoprotein, Helicobacter pylori, immunity, Immunization, Influenza, Microscopy, Nanoparticle, Nanoparticles, Pandemic, Protein, Protein Expression, Rabies, Receptor, Research, Respiratory, SARS, SARS-CoV-2, Severe Acute Respiratory, Severe Acute Respiratory Syndrome, Spike Protein, Syndrome, Vaccine, Virus, Western Blot

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Shanet Susan Alex

Shanet Susan Alex, a medical writer, based in Kerala, India, is a Doctor of Pharmacy graduate from Kerala University of Health Sciences. Her academic background is in clinical pharmacy and research, and she is passionate about medical writing. Shanet has published papers in the International Journal of Medical Science and Current Research (IJMSCR), the International Journal of Pharmacy (IJP), and the International Journal of Medical Science and Applied Research (IJMSAR). Apart from work, she enjoys listening to music and watching movies.

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