Nanoparticle-delivered COVID-19 vaccine candidate shows promise in preclinical studies

CLEVELAND – Researchers from the Cleveland Global Clinic Center for Pathogen Research & Human Health have developed a promising new COVID-19 vaccine candidate that uses nanotechnology and has demonstrated strong efficacy in preclinical disease models.

According to new results published in mBio, the vaccine produced strong neutral antibodies among preclinical models and prevented the symptoms of infection and disease against exposure to SARS-CoV-2 (the virus that causes COVID-19). An additional reason for the early appeal of the vaccine applicant is that it may be thermostable, which would make it easier to carry and store than the currently authorized COVID-19 vaccines.

“Our vaccine candidate delivers antigens to stimulate an immune response through nanoparticles engineered from ferritin – a protein found in almost all organisms,” said Jae Jung, PhD, director of the Global Center for Ferritin. Human Health & Pathogen Research and co – author of the study. “This protein is an attractive biomaterial for vaccine and drug delivery for many reasons, given that it does not require strict temperature control. ”

Added Dokyun (Leo) Kim, a graduate student in Dr. Jung’s laboratory and co-author of the study, “This would greatly reduce shipping and storage restrictions, which are the challenges we currently face in efforts It would also be beneficial to distribute it to developing countries. “

Other benefits of the protein nanoparticles include reducing cell damage and providing stronger immunity at lower doses than traditional protein subunit vaccines against other viruses, such as influenza.

The team’s vaccine uses the ferritin nanoparticles to deliver tiny particles from the SARS-CoV-2 spike protein segment that selectively binds to the human entry point for the virus (this piece is called the field receptor binding, or RBD). When the SARS-CoV-2 RBD binds to the human protein called ACE2 (angiotensin-converting enzyme 2), the virus can enter host cells and begin to reproduce.

The researchers tested their vaccine candidate on a ferret model of COVID-19, which exhibits a better human immune response and disease development than other preclinical models. Professor Jung, a leading authority in virology and virus-induced cancers, has developed the world’s first COVID-19 ferret model – a discovery that has led to advanced research on SARS-CoV-2 infection and transmission .

In this study, the researchers administered an initial dose of the vaccine candidate and then two booster vaccines given 14 and 28 days later. One group received the vaccines intramuscularly, and another group received them both intramuscularly and intranasally.

After the second increase, all vaccine models yielded strong neutral antibodies. This suggests that exposure to the RBD antigen successfully prepared the immune systems to quickly fight the virus.

A few days after the second increase (31 days after the first vaccine dose), the researchers exposed the models to high concentrations of SARS-CoV-2. Compared with the placebo group that received only adjuvant vaccines (confession is an ingredient that helps vaccines work better), those who received the RBD-nanoparticle vaccine were better protected from clinical symptoms and lung damage. associated with disease. The findings show that the candidate of the vaccine helped prevent infection and serious infection.

Intramuscular and intranasal vaccinations showed a combination of stronger immunosuppression and faster viral clearance than intramuscular vaccination alone. Both were significantly more effective than the adjuvant vaccine alone. More research will be important to find out the tools behind these different benefits.

Although ferritin nanoparticles are well-characterized for their strong temperature and chemical stability, suggesting that the RBD-nanoparticle vaccine may also be thermostable, future studies will be needed to confirm. The researchers aim to confirm these findings in human clinical trials soon.

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This study was a close collaboration between Dr. Jung and researchers from Chungbuk National University in South Korea – including co-author Young Ki Choi, PhD, and co-author Young- Il Kim, PhD – and was supported in part. with the National Institutes of Health.