Nanoparticle-Delivered COVID-19 Vaccine Candidate Shows Promise in Preclinical Studies



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March 02, 2021

(Nanowerk News) Researchers at the Cleveland Clinic Global Center for Pathogen Research and Human Health have developed a promising new vaccine candidate for COVID-19 that uses nanotechnology and has shown great efficacy in preclinical disease models.

According to new findings published in mBio (“Development of spike receptor-binding domain nanoparticles as a candidate vaccine against SARS-CoV-2 infection in ferrets”), the vaccine produced potent neutralizing antibodies between preclinical models and also prevented infection and symptoms of the disease versus exposure to SARS. CoV-2 (the virus that causes COVID-19). An additional reason for the early appeal of the candidate vaccine is that it may be heat stable, making it easier to transport and store than currently licensed COVID-19 vaccines.

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

Dokyun (Leo) Kim, a graduate student in Dr. Jung’s lab and a co-author of the study, added: “This would dramatically alleviate shipping and storage limitations, which are challenges we are currently experiencing in national distribution efforts. beneficial for distribution to developing countries “.

Other benefits of protein nanoparticles include minimizing 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 ferritin nanoparticles to release tiny, weakened fragments of the peak protein region of SARS-CoV-2 that selectively binds to the human entry point of the virus (this fragment is called the receptor-binding domain or RBD). . When SARS-CoV-2 RBD binds to the human protein called ACE2 (angiotensin-converting enzyme 2), the virus can enter host cells and begin to replicate.

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

In this study, researchers administered an initial dose of the candidate vaccine followed by two booster vaccines given 14 and 28 days later. One group received the vaccines intramuscularly, while another group received both intramuscular and intranasal routes.

After the second boost, all vaccinated models produced strong neutralizing antibodies. This suggests that repeated exposure to the RBD antigen successfully primed the immune system to rapidly fight the virus.

A few days after the second booster (31 days after the initial dose of the vaccine), the researchers exposed the models to high concentrations of SARS-CoV-2. Compared to the placebo group that received adjuvant-only vaccines (adjuvants are added ingredients that help vaccines work better), those that received the RBD nanoparticle vaccine were better protected from clinical symptoms and lung damage associated with the infection. The findings suggest that the candidate vaccine helped prevent serious infections and illnesses.

Combined intramuscular and intranasal immunization showed stronger protective immunity and faster viral clearance than intramuscular immunization alone. Both were significantly more effective than the adjuvanted vaccine alone. More research will be important to discover the mechanisms behind these differential benefits.

While ferritin nanoparticles are well characterized by their strong temperature and chemical stability, suggesting that the RBD nanoparticle vaccine may also be heat stable, future research will need to be done to validate them. The researchers intend to soon confirm these findings in human clinical trials.

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