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The University of California San Diego has developed COVID-19 vaccine candidate candidates. These vaccine candidates can withstand heat. What are their key ingredients? Viruses that are derived from bacteria or plants.
The development of the new refrigerator-free COVID-19 vaccines is still in its early stages. The vaccine candidates in mice triggered high levels of neutralizing antibodies against SARS-2, which is the virus responsible for COVID-19. The vaccines can be an important game changer in global distribution efforts, especially in rural areas and resource-poor communities, if they are safe and effective in humans.
"What's exciting about our vaccine technology is that is thermally stable, so it could easily reach places where setting up ultra-low temperature freezers, or having trucks drive around with these freezers, is not going to be possible," said Nicole Steinmetz, a professor of nanoengineering and the director of the Center for Nano-ImmunoEngineering at the UC San Diego Jacobs School of Engineering.
In a Sept. 7 paper in the Journal of the American Chemical Society, the vaccines are described in detail.
Two COVID-19 vaccine candidates were created by the researchers. The first is made from cowpea mosaic virus, a plant virus. The second is made of a bacterial virus or bacteriophage called Q beta.
Both vaccines were prepared using the same recipes. Researchers used cowpea plants to make millions of copies of the plant virus, and E.coli bacteria to create nanoparticles in the ball-shaped form. These nanoparticles were then harvested by the researchers, who attached a small amount of the SARS-2 spike protein to their surface. They look like an infectious virus, so the immune system can recognize them. However, they are not infective in humans and animals. The body generates an immune response against coronavirus by attaching a small amount of spike protein to the surface.
Researchers note many benefits to using plant viruses and bacteria to create their vaccines. They are easy to make at large scales and can be inexpensive. Steinmetz stated that growing plants is easy and requires minimal infrastructure. "Fermentation using bacteria is an established process in biopharmaceutical manufacturing."
The plant virus and bacteriophage nanparticles are also extremely stable at high temperatures. The vaccines can therefore be shipped and stored without the need to be kept cool. You can also heat-process them. This team uses such processes to package vaccines into microneedle patches and polymer implants. Mixing the vaccine candidates with polymers is done by melting them in an oven at close to 100° Celsius. It is easy to make vaccine patches and implants by mixing the bacteriophage and plant virus nanoparticles directly with the polymers.
This is to make it easier for people to get the COVID-19 vaccine. Implants are placed under the skin and gradually release the vaccine over the course a month. Only one dose is required. The microneedle patches can be worn on the arm and are painless. This would allow the user to self-administer vaccines.
Jon Pokorski, a professor of Nanoengineering at UC San Diego Jacobs School of Engineering who developed the technology for the microneedle patches and implants, said, "Imagine if vaccines could be sent directly to the mailboxes of the most vulnerable people."
Pokorski, who is also a founder faculty member of the university’s Institute for Materials Discovery and Design, said, "If clinics could offer one-dose implants to those who would have really difficult time making it out for the second shot, that would offer protection for the entire population and we could have better chances at stemming transmission."
The COVID-19 vaccine candidates from the team were administered to mice via microneedle patches or implants. All three methods resulted in high levels of neutralizing antibodies that were detected in blood cells against SARS-CoV-2.
Potential pan-coronavirus vaccine
Researchers found that the same antibodies were also effective in neutralizing the SARS virus.
The coronavirus spike protein is what attaches to the surface of nanoparticles. Steinmetz's team selected an epitope as one of the pieces. It is nearly identical to SARS-CoV-2 virus.
"The fact that neutralization with an epitope so well conserved among other deadly coronaviruses is so profound is amazing," co-author Matthew Shin, a student in Steinmetz’s laboratory of nanoengineering. This gives us hope for a pan-coronavirus vaccine, which could provide protection against future pandemics.
This epitope also has the advantage that it isn't affected by any SARS-CoV-2 mutations. This is because the epitope is not directly bound to cells and comes from a spike protein region. This epitope is not found in COVID-19 vaccines. They come from the spike protein binding region. This region is where many mutations have occurred. Some of these mutations have made it more contagious.
Oscar Ortega-Rivera is a postdoctoral researcher at Steinmetz's laboratory and the study's first writer. "Based on sequence analysis, we found that the epitope we selected is highly conserved among the SARS-CoV-2 variations."
Ortega-Rivera stated that this means that the COVID-19 vaccines may be effective against some variants of concern. Currently, tests are underway to determine if they have any effect against the Delta variant.
Plug and Play Vaccine
Steinmetz is also excited by the flexibility it gives to create new vaccines. Steinmetz stated that even if the technology doesn't make an impact on COVID-19 it can be easily adapted to the next threat, which is virus X.
She says it is easy to make these vaccines: first, grow plant virus or bacteria nanoparticles and then attach a small piece of the target virus, pathogen or biomarker on the surface.
"We use the exact same nanoparticles, polymers and chemistry to put it all together. Steinmetz stated that the only thing that can be changed is the antigen we use to stick to the surface.
The vaccines are not required to be kept at room temperature. You can package them into microneedle patches or implants. They can also be administered directly via shots.
This recipe has been used in the past by Pokorski and Steinmetz's labs to create vaccine candidates for diseases such as cholesterol and HPV. They have now shown it can be used to make COVID-19 vaccine candidate candidates.
Next steps
There is still much to be done before the vaccines can make it to clinical trials. The team will now test the vaccines in vivo to see if they are effective against COVID-19 and its variants.
Investigate further Marrying molecular agriculture and advanced manufacturing for a COVID-19 vaccination
More information: Trivalent Subunit Vaccine Candidates for COVID-19, and their Delivery Devices, Journal of the American Chemical Society (2021). Journal Information: Journal of the American Chemical Society. Trivalent subunit vaccine candidates and their delivery devices for COVID-19. DOI: 10.1021/jacs.1c06600
