Self-assembled candidate nanoparticles are an effective vaccine for SARS-CoV-2

COVID-19 (coronavirus disease 2019) is caused by advanced new coronavirus RNA, acute coronavirus 2 respiratory syndrome (SARS-CoV-2), which belongs to the family Coronaviridae. To date, more than 117 million people have been infected with SARS-CoV-2 worldwide, including nearly 2.6 million deaths. The staggering number of SARS-CoV-2 patients has devastated healthcare facilities around the world.

Strong protective measures are needed to control the pandemic, mitigate the viral spread, and stop its devastating effects. While coronaviruses usually circulate in humans and cause a common cold, vaccines were not contraindicated until COVID-19 pandemic. At an unprecedented pace, SARS-CoV-2 vaccines have been developed and delivered worldwide.

The SARS-CoV-2 viral envelope is crowned by the highly glycosylated protein Spike (S) protruding from the virion surface. This is the critical bridge between the virus and the host cell, playing an important role in host cell receptor identification, virion binding, and ultimately access to the host cell. The S1 subunit of the S protein provides specificity in cell tropism through its receptor binding domain (RBD). Therefore, the RBD is the main target for developing vaccine candidates.

Vaccines currently being developed against SARS-CoV-2 contain the RBD in their immunogen. With a similar goal, a new study developed an RBD protein-based vaccine candidate against the SARS-CoV-2, using autophagy Helicobacter pylori-bullfrog ferritin nanoparticles as an antigen delivery system. The study is recently published in the journal mBio (by American Society of Microbiology).

In this study, a collaborative team from the Republic of Korea and the US described this new vaccine candidate – Spike receptor-binding nanoparticles – for the SARS-CoV-2 infection. They have demonstrated the study in ferrets with remarkable neutral activity against SARS-CoV-2.

The researchers cleared the RBD-nanoparticle from transplanted HEK293T cells and vaccinated the ferrets through the intramuscular (im) and intranasal (inward) pathways. They monitored the entry of neutralizing antibodies. They then challenged the ferrets vaccinated with SARS-CoV-2 and checked their immunity against the SARS-CoV-2.

Interestingly, the researchers found that the vaccinated muscles showed effective protection from SARS-CoV-2 challenge, without fever, body weight loss, or clinical symptoms. They also observed rapid clearance of infectious virus in nasal and lung washes and viral RNA in respiratory organs.

“Animals vaccinated intramuscularly showed strong induction of antibody neutralization, rapid clearance of respiratory tract virus, and removal of clinical symptoms, which is further enhanced in conjunction with intranasal vaccination. ”

Because ferrets are naturally susceptible to human respiratory viruses, the researchers in this study used ferrets as a unique model for the study of respiratory virus infections in humans. Also, the ferrets share with humans the anatomy of the upper and lower respiratory tract, the architecture of terminal bronchioles, and the density of the submucosal glands. Unlike the current human transtgenic mouse model ACE2 (hACE2), the SARS-CoV-2-infected mice have shown similar immune responses and pathogenic progression and shed the virus through the nasal, saliva, urine, and fecal wash samples, which repeat the human SARS-CoV-2 infection.

The latest advances in molecular biology and nanotechnology have recently embraced nanoparticle engineering as a platform for vaccines – to design small virus-like particles. It is established that the human immune system reacts effectively only against immunogens of nanometer range in size. Therefore, the efficacy of these vaccines with nanoparticle engine is also reported to be higher than compared to the traditional vaccines.

The researchers used nanoparticle-based vaccines because of their immunological benefit: efficient transport of antigen to lymph node drainage and antigen presentation by follicular and T helper dendritic cells and high levels of activation of germinal centers .

Ferritin is a genetically engineered nanoparticle with a natural tendency to automatically accumulate into a 24-meric homopolymer. Due to its convenience through fusion peptides, ferritin is highly stable as an excellent candidate for drug delivery and vaccine development.

For this study, the researchers used one of the recently invented ferritins for vaccine development. The self-assembled Helritobacter pylori-bullfrog hybrid ferritin (Rana catesbeiana) carries NH₂-lives from the lower base of ferritin bullfrog on the heart of the Helicobacter pylori ferritin to form radically rising tails.

“The H. pylori ferritin-based nanoparticle has been reported to be an effective platform for vaccines to transport trimeric glycoproteins for the expression of viral immunogens on its 3-fold axis points. “

In another method of vaccination against SARS-CoV-2, the researchers used a well-targeted nanotechnology approach to produce safer and more powerful vaccines.

This study demonstrated the immunogenic efficacy of the RBD-ferritin self-assembled spike nanoparticle (RBD-nanoparticle) as an effective SARS-CoV-2 vaccine antigen.

The researchers investigated the vaccine potential of the RBD-nanoparticles by challenging the vaccine ferrets with high virus titer. They found that the vaccinated ferrets showed significantly reduced clinical symptoms, such as body weight loss, cough, runny nose, and movement activity, challenged with high-titer SARS-CoV-2.

Based on the findings of this study, the researchers proposed the self-assembled RBD-nanoparticles as a vaccine candidate that could effectively protect against SARS-CoV-2 infection. This requires further studies in addition to the proposed vaccine candidate to understand humoral and cellular immunity.