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Self-assembled nanoparticles are effective vaccine candidates for SARS-CoV-2

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COVID-19 (Coronavirus Disease 2019) is caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), a new plus-strand RNA coronavirus belonging to the Coronavirus family. To date, more than 117 million people worldwide have been infected with SARS-CoV-2, of which nearly 2.6 million have died. The overwhelming number of SARS-CoV-2 patients have destroyed medical resources around the world.

Strong precautions are needed to control the pandemic, mitigate viral infections and stop their devastating effects. Coronaviruses generally circulate in humans and cause common colds, but there was no vaccine against them until the COVID-19 pandemic. At an unprecedented pace, the SARS-CoV-2 vaccine was developed and administered worldwide.

The SARS-CoV-2 virus envelope is coronary with highly glycosylated spike (S) proteins protruding from the surface of the virion. It is an important bridge between the virus and the host cell and plays an important role in host cell receptor recognition, virion attachment, and ultimately invasion of the host cell. The S1 subunit of the S protein confers cell orientation through its receptor binding domain (RBD). Therefore, RBD is a major target for the development of vaccine candidates.

Currently developing vaccines against SARS-CoV-2 contain RBD as an immunogen.For a similar purpose, a new study used self-organization to develop RBD protein-based vaccine candidates for SARS-CoV-2. Helicobacter pylori-Bullfrog ferritin nanoparticles as an antigen delivery system.This study was recently published in a journal mBio (According to the American Society for Microbiology).

Design and purification of RBD nanoparticles. (A) H. Computer-assisted modeling of RBD nanoparticles based on previously resolved structures of pylori ferritin (PDB accession number 3EGM) and SARS-CoV-2 RBD (PDB accession number 7JMP). RBD forms radial protrusions at the triple axis of fully assembled nanoparticles. (B) Coomassie blue staining of purified ferritin nanoparticles and RBD nanoparticles after SDS-PAGE. (C) Size-exclusion chromatography peak of concentrated supernatants from HEK293T cells transfected with a plasmid encoding secreted ferritin or RBD nanoparticles. The supernatant was concentrated on a 100 kDa-MWCO and 500 kDa-MWCO filter with a TFF system and loaded onto Bio-Rad NGC Superdex 200 Increased 10/300 GL and HiPrep 16/60 Cefacryl S-500HR gel filtration columns. Chromatography system respectively. mAU, arbitrary unit (thousand units).

In this study, a joint team from the Republic of Korea and the United States reported spike receptor-binding nanoparticles, a new vaccine candidate for SARS-CoV-2 infection. They demonstrated studies with ferrets that have significant neutralizing activity against SARS-CoV-2.

Researchers purified RBD nanoparticles from transfected HEK293T cells and immunized ferrets via the intramuscular (im) and intranasal (in) pathways.They monitored the guidance of Neutralizing antibody.. Next, SARS-CoV-2 was administered to the vaccinated ferrets, and protective immunity against SARS-CoV-2 was observed.

Interestingly, the researchers observed that vaccinated ferrets showed efficient protection from the SARS-CoV-2 challenge without fever, weight loss, or clinical symptoms. They also observed rapid clearance of infectious virus in the nasal lavage fluid and lungs and viral RNA in the respiratory tract.

“Intramuscular immunized animals showed strong induction of neutralizing antibodies, rapid clearance of respiratory track virus, and clear suppression of clinical symptoms that were further enhanced in combination with intranasal immunity.”

Because ferrets are naturally susceptible to human respiratory virus infections, researchers in this study used ferrets as an ideal model for studying human respiratory virus infections. Ferrets also share with humans the anatomical structure of the upper and lower airways, the structure of the terminal bronchioles, and the density of submucosal glands. Unlike current human ACE2 (hACE2) transgenic mouse models, SARS-CoV-2 infected ferrets exhibit a human-like immune response and pathogenic progression through nasal lavage fluid, saliva, urine, and fecal samples. Eliminates the virus. Summarizes human SARS-CoV-2 infection.

The latest advances in molecular biology and nanotechnology have recently adopted nanoparticle engineering, which acts as a vaccine platform. This is for designing small virus-like particles. The human immune system has been established to respond efficiently only to immunogens sized in the nanometer range. Therefore, the following is also reported: Effectiveness of These nanoparticle engineering vaccines are superior to traditional vaccines.

Researcher used Nanoparticle-based vaccine Due to their immunological benefits: efficient antigen transport to influx area lymph nodes, antigen presentation by follicular dendritic cells and helper T cells, and high levels of germinal center activation.

Ferritin is a well-characterized genetically engineered nanoparticles with a natural tendency to self-assemble into 24-mer homopolymers. Highly stable ferritin is an ideal candidate for drug delivery and vaccination development due to its susceptibility to fusion peptides.

In this study, researchers used one of the ferritins recently designed for vaccine development.Self-organizing Helicobacter pylori bullfrog (Rana catesbeiana) hybrid ferritin carries NH2-Terminal residues of the lower subunit of bullfrog ferritin Helicobacter pylori Ferritin that forms a radially protruding tail.

“H. pyrroliferitin-based nanoparticles have been reported to be an effective platform for vaccines to carry trimer glycoproteins to present viral immunogenicity at their triple axis.”

In an alternative vaccine approach to SARS-CoV-2, researchers used a well-characterized nanotechnology approach to produce safer and more potent vaccines.

This study demonstrated the immunogenicity efficacy of self-assembling spike RBD-ferritin nanoparticles (RBD-nanoparticles) as an efficient SARS-CoV-2 vaccine antigen.

Researchers have investigated the potential of RBD nanoparticles to vaccinate by challenging immunized ferrets with high viral titers. They found that when immunized ferrets were challenged with the high titer SARS-CoV-2, clinical symptoms such as weight loss, cough, runny nose, and motor activity were significantly reduced.

Based on the observations of this study, the researchers proposed self-assembled RBD nanoparticles as potential vaccine candidates that could effectively protect against SARS-CoV-2 infection. This requires further research on the vaccine candidates proposed to understand humoral and cell-mediated immunity.

Journal reference:

  • Development of spike receptor binding domain nanoparticles as vaccine candidates for SARS-CoV-2 infection in ferrets, Kim Young-il, Kim Do-kyun, Yu Kwang-min, Seo Ho-gyu David, Lee Shin-ae, Mark Anthony B・ Kazel, Seung-Gyu Jang, Stephanie Kim, WooRam Jung, Chih-Jen Lai, Young Ki Choi, Jae U. Jung, mBio March 2021, 12 (2) e00230-21; DOI: 10.1128 / mBio.00230-21, https://mbio.asm.org/content/12/2/e00230-21

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