The COVID-19 vaccine rollout has been mired in logistical challenges. Millions of doses have gone to waste, some spoiling after being left unrefrigerated for too long, some expiring before they could physically get to those in need. Most of the vaccines need to be kept at incredibly low temperatures, requiring a cold chain for distribution, a tricky feat when the vaccine needs to access remote areas or regions without electricity. Even with the vaccines in place, you still need people to put those shots in arms, and to come back and do it all again for the second dose.
Nicole Steinmetz, a professor of nanoengineering and the director of the Center for Nano ImmunoEngineering at the University of California, San Diego (UCSD), imagines another way: “thermally stable” vaccines that don’t need to be transported in freezers, and which could come in a microneedle patch—so that “you could ship it to people’s homes, and they can self-administer just like a bandaid,” she says—or in one-dose implants, eliminating the need to set up a second appointment.
For Steinmetz, this vision of a vaccine rollout is more than a dream. In a paper recently published in the Journal of the American Chemical Society, she and her team detail the developments they’ve made toward fridge-free COVID-19 vaccines made with viruses from plants or bacteria. In mice, the paper details, these vaccine candidates triggered the production of SARS-CoV-2-neutralizing antibodies. “The levels [of antibodies generated] we report are comparable to what Moderna reported in its preclinical work,” Steinmetz says.
Current COVID vaccines need to be frozen so that the mRNA—and the lipid nanoparticles that protect the mRNA and help it get into cells—don’t break down. (The Moderna vaccine is shipped between minus 58 degrees Fahrenheit and 5 degrees Fahrenheit; Pfizer‘s vaccine arrives between minus 130 degrees Fahrenheit and minus 76 degrees Fahrenheit, and both last in a fridge for only a month.) The UCSD-developed vaccine candidates do not use mRNA or lipid particles, but are instead subunit vaccines, which means they contain a fragment of the pathogen’s protein.
The researchers created two options, one made from a plant virus, and another made from a bacterial virus; they grew copies of those viruses into a cluster of nanoparticles, and then a fragment of the SARS-CoV-2 spike protein was attached to the surface of the nanoparticles. “In our case, we’re not using the full length spike protein, we’re just using . . . snippets of the S protein, and we’ve narrowed it down to a few sequences that are recognized by the immune system and illicit neutralizing antibody responses,” she says.
The plant and bacterial viruses are not infectious for humans, Steinmetz says, and have also adapted to withstand environmental conditions like various temperatures, which is what makes them fridge-free. “Even though the plant virus is not infectious toward a human, it still to the immune system looks like a virus, so it makes a good immune stimulator.”
The researchers went a step further to formulate the vaccine into slow-release formulas, including a single shot, a microneedle patch, and a one-time implant. “For rural areas in the world, it’s really challenging to set up mobile doctors’ offices to get people vaccinated, and it might be challenging to do that twice,” she says, so single-shot vaccines or an implant could make patient compliance easier. The same goes for patches, which could be shipped or “dropped anywhere in the world” without the need to set up a cold-storage chain, and which could hopefully get more people vaccinated more quickly.
The concept of using viruses to make a vaccine is not new, but vaccines of bacterial- or plant-based viruses have not yet been used in humans. The development of these vaccines is still in its early stages, and Steinmetz is realistic that they might not be ready to make an impact on COVID-19. But the work being done now could set the stage for more rapid vaccine development in the face of another pandemic.
“If you look at Moderna and Pfizer, they were the first to be ready with vaccines, but they hadn’t been working on a COVID-19 vaccine before the pandemic. They’ve been developing technology for mRNA vaccines, so they were ready when the pandemic hit,” she says. “This is where I see our technology. We now have all the building blocks in place.” She calls it a “plug-and-play technology” because that snippet of SARS-CoV-2 attached to the plant or bacterial viruses could easily be replaced with a piece of another pathogen. “When the next challenge hits—it could be a local epidemic somewhere where you need something heat-stable or something that could be self administered—then the technology would be ready to do this plug-and-play, and have this readiness for the next virus.”