The vaccine produced potent neutralizing antibodies among preclinical models and also prevented infection and disease symptoms in the face of exposure to SARS-CoV-2, according to new findings published in mBio.
SARS-CoV-2, a causative agent of the COVID-19 pandemic, enters host cells via the interaction of its receptor-binding domain (RBD) of the spike protein with host angiotensin-converting enzyme 2 (ACE2). Therefore, the RBD is a promising vaccine target to induce protective immunity against SARS-CoV-2 infection, said the team behind the work.
Dr Jae Jung, director of the Global Center for Human Health & Pathogen Research and co-senior author on the study, said the vaccine candidate delivers antigens to trigger an immune response via nanoparticles engineered from ferritin-a protein found in almost all living organisms. "This protein is an attractive biomaterial for vaccine and drug delivery for many reasons, including that it does not require strict temperature control."
Ferritin nanoparticles are well-characterized for their strong temperature and chemical stability, suggesting the RBD-nanoparticle vaccine may be thermostable, the researchers explained.
The investigational vaccine may be therefore easy to transport and store but the team said further investigations are required to validate that the vaccine is thermostable.
They aim to confirm their findings in human clinical trials soon.
Other benefits of the protein nanoparticles include minimizing cellular damage and providing stronger immunity at lower doses than traditional protein subunit vaccines against other viruses, like influenza, said the research team.
How it works
Their vaccine uses the ferritin nanoparticles to deliver tiny, 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 (RBD).
When the SARS-CoV-2 RBD binds with the human protein called angiotensin-converting enzyme 2 (ACE2), the virus can enter host cells and begin to replicate, they said.
The researchers said they tested their vaccine candidate on a ferret model of COVID-19, which they said reflects the human immune response and disease development better than other preclinical models.
Dr Jung, deemed an authority in virology and virus-induced cancers, previously developed the world's first COVID-19 ferret model - a discovery that is said to have advanced research into SARS-CoV-2 infection and transmission.
The researchers administered an initial dose of the vaccine candidate followed by two booster vaccines given 14 and 28 days later. One group received the vaccines intramuscularly, while another group received them both intramuscularly and intranasally.
After the second booster, all vaccinated models produced strong neutralizing antibodies, they found. “This suggests that repeated exposure to the RBD antigen successfully prepared the immune systems to rapidly fight the virus.”
A few days after the second booster - 31 days after the initial vaccine dose - the researchers exposed the models to high concentrations of SARS-CoV-2.
“Compared to the placebo group that received adjuvant-only vaccines, those that received the RBD-nanoparticle vaccine were better protected from clinical symptoms and lung damage associated with infection. The findings suggest the vaccine candidate helped prevent infection and serious disease.”
Combination intramuscular and intranasal immunization showed more potent protective immunity and faster viral clearance than intramuscular immunization alone. Both were significantly more effective than the adjuvant-only vaccine.
More research will be important to uncover the mechanisms behind these differential benefits, said the team.
"Additional comprehensive studies are needed to understand the humoral and cellular immunity elicited by RBD-nanoparticle administration and differential activation of IgA-mediated mucosal immunity by different immunization routes. Taken together, our study indicated that immunization with self-assembling SARS-CoV-2 RBD-nanoparticles elicits protective immunity against SARS-CoV-2 infection, showing its potential as a vaccine candidate in the midst of the COVID-19 pandemic."
Dr Jung collaborated with researchers from Chungbuk National University in South Korea on the study.
Title: Development of Spike Receptor-Binding Domain Nanoparticles as a Vaccine Candidate against SARS-CoV-2 Infection in Ferrets
Authors: Y-Il Kim, D Kim, K-M Yu, HD Seo, S-A Lee, MA B Casel, S-G Jang, S Kim, WR Jung, C-Jen Lai, Y Ki Choi, J U Jung