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Ferrets and gourds

Nano-delivered Covid-19 vaccine candidate shows promise in ferrets

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Researchers from Cleveland Clinic have developed a new Covid-19 vaccine candidate which utilises nanotechnology for delivery. The candidate has shown promising results in preclinical disease models.

The vaccine produced potent neutralising antibodies in preclinical models, preventing infection and disease symptoms when exposed to the novel coronavirus SARS-CoV-2.

“Our vaccine candidate delivers antigens to trigger an immune response via nanoparticles engineered from ferritin: a protein found in almost all living organisms,” said Dr Jae Jung, director of the Global Centre for Human Health & Pathogen Research at Cleveland Clinic. “This protein is an attractive biomaterial for vaccine and drug delivery for many reasons, including that it does not require strict temperature control.”

The vaccine candidate may be thermostable; if this is confirmed, this would make it an appealing option as it would be far easier to transport and store than the approved Covid-19 vaccines being distributed presently.

Leo Kim, a graduate student and co-first author on the study, commented: “This would dramatically ease shipping and storage constraints, which are challenges we’re currently experiencing in national distribution efforts. It would also be beneficial for distribution to developing countries.”

Other benefits of the protein nanoparticles include minimising cellular damage and providing stronger immunity at lower doses than conventional vaccines of this type used against other viruses, such as influenza.

The vaccine uses the ferritin nanoparticles to deliver weakened fragments from the region of the SARS-CoV-2 spike protein that selectively binds to the human 'entry point' for the virus (the receptor-binding domain). When the SARS-CoV-2 receptor-binding domain binds with the human protein ACE2, the virus can enter host cells and start replicating.

The researchers trialled the vaccine candidate in a ferret model of Covid-19 which reflects the immune response and disease development in humans more closely than other preclinical models. They administered an initial dose of the vaccine candidate, followed by two boosters given 14 and 28 days later. One group received them intramuscularly and the other received them both intramuscularly and intranasally.

Following the second booster, all vaccinated models produced strong neutralising antibodies, suggesting that repeated exposure to the receptor-binding domain antigen successfully prepared the ferrets’ immune systems to fight the virus effectively.

Three days after the second booster was administered, the ferrets were exposed to high concentrations of SARS-CoV-2. Compared to the placebo group, those who received the vaccine candidate were better protected from clinical symptoms and lung damage associated with the disease, while those that received theirs via both intramuscular and intranasal application had the strongest protection and fastest viral clearance.

Ferritin nanoparticles are known for their strong temperature and chemical stability. This could allow for the development of a thermostable vaccine, depending on the results of future investigations. The researchers hope to replicate their findings in human clinical trials soon.

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