Scientists are continuing to explore fresh ways to deliver COVID-19 vaccinations, including recent research into so-called mosaic nanoparticles and easy-to-store inhaled options.
Researchers led by Caltech's Pamela Bjorkman, Ph.D., investigated the use of a mosaic vaccine, which presents the immune system with pieces of the spike protein from SARS-CoV-2 as well as seven other SARS-like betacoronaviruses. These are attached to a protein nanoparticle structure in order to induce the production of a broad spectrum of cross-reactive antibodies.
The team used vaccine technology first developed at the University of Oxford that allows for either one or multiple viruses to attach to a nanoparticle, a tiny cagelike structure of proteins with sticky appendages.
In their paper published July 5 in the journal Science, the researchers noted that mice vaccinated with their mosaic nanoparticle were not only protected from the eight viruses represented in the vaccine, but also the SARS-CoV virus responsible for the severe acute respiratory syndrome (SARS) outbreaks in 2002 and 2004.
The mice were genetically engineered to express the human ACE2 receptor, which is the receptor on human cells used by SARS-CoV-2 and related viruses to gain entry into cells. Primates that received the vaccine showed similar results to the mice.
"Animals vaccinated with the mosaic-8 nanoparticles elicited antibodies that recognized virtually every SARS-like betacoronavirus strain we evaluated," said the study’s first co-author Alexander Cohen, Ph.D. "Some of these viruses could be related to the strain that causes the next SARS-like betacoronavirus outbreak, so what we really want would be something that targets this entire group of viruses. We believe we have that."
Bjorkman said that the fact that three betacoronaviruses—SARS-CoV, MERS-CoV, and SARS-CoV-2—have spilled over into humans from animal hosts in the last 20 years "illustrates the need for making broadly protective vaccines."
"What we're trying to do is make an all-in-one vaccine protective against SARS-like betacoronaviruses regardless of which animal viruses might evolve to allow human infection and spread," she explained. "This sort of vaccine would also protect against current and future SARS-CoV-2 variants without the need for updating."
The next step for the team will be tests on animals that have already received an existing COVID-19 vaccine, ahead of a phase 1 clinical trial supported by the Coalition for Epidemic Preparedness Initiative to assess the mosaic vaccine in previously COVID-19 vaccinated or infected humans.
Inhaled vaccine with easy storage
Meanwhile, researchers at the University of North Carolina-North Carolina State University’s Joint Department of Biomedical Engineering, along with colleagues from Duke University, are developing an inhalable COVID-19 vaccine that can be stored at room temperature for up to three months. The vaccine’s delivery mechanism is a lung-derived exosome called LSC-Exo, which is more effective at evading the lung’s mucosal lining than the lipid-based nanoparticles currently in use, the researchers announced July 5.
The inhaled vaccine can also be used effectively with protein-based vaccines, they added.
“There are several challenges associated with vaccine delivery we wanted to address,” said Ke Cheng, Ph.D., who led development of the vaccine prototype and the proof-of-concept animal studies.
“First, taking the vaccine via intramuscular shot is less efficient at getting it into the pulmonary system, and so can limit its efficacy. Inhaled vaccines would increase their benefit against COVID-19,” he said.
“Second, mRNA vaccines in their current formulation require cold storage and trained medical personnel to deliver them. A vaccine that is stable at room temperature and that could be self-administered would greatly reduce wait times for patients as well as stress on the medical profession during a pandemic.”
Inhaled COVID-19 vaccines have long been a goal for Big Pharma, with the University of Oxford and CanSino both putting assets into clinical trials.