Currently available COVID-19 vaccines come in the form of one or two injections and must be stored and transported at low- or ultra-low temperatures in order to remain stable and effective. This temperature requirement poses challenges in areas where ultra-low temperature freezers are not widely available and precludes delivery methods that involve high temperatures in the manufacturing process. Nanoengineers at the University of California San Diego are working to develop new COVID-19 vaccines derived from a plant virus and bacteriophage that are thermally stable enough to be easily transported around the globe and even be delivered through a single patch or implant.
The two COVID-19 vaccine candidates are in the early stage of development and so far have been shown to trigger high production of neutralizing antibodies against SARS-CoV-2 in mice. One of the candidates is made from cowpea mosaic virus and the other comes from Q beta, which is grown in E. coli. Both viruses are thermally stable and not infectious in animals and humans, but when grown in nanoparticles and combined with a piece of the SARS-CoV-2 spike protein, they can elicit an immune response that protects the body from further SARS-CoV-2 infection.
The researchers specifically chose an epitope that is almost identical between SARS-CoV-2 and the original SARS virus, producing antibodies that protect against both. And because this epitope comes from a region of the spike protein that does not bind directly to cells, it is less likely to be affected by mutations, which occur more often in the protein’s binding region.
Due to the ability for these plant and bacterial viruses to withstand high temperatures, the candidate vaccines can be combined with polymers and melted down to create an implant or microneedle patch as an alternative method of vaccine administration. A polymer implant could be injected under the skin to slowly release the vaccine over the course of a month, while a patch could allow the wearer to easily and comfortably self-administer the vaccine without even leaving home. The researchers tested their vaccine candidates in mice using either an implant, patch or series of two shots, and found that all three methods produced high levels of neutralizing antibodies against SARS-CoV-2. This research was published in the Journal of the American Chemical Society.
“Imagine if vaccine patches could be sent to the mailboxes of our most vulnerable people, rather than having them leave their homes and risk exposure,” said Jon Pokorski, whose team developed the implant and microneedle patch technologies for the study. “If clinics could offer a one-dose implant to those who would have a really hard time making it out for their second shot, that would offer protection for more of the population and we would have a better chance at stemming transmission.”
Researchers noted that even if the technology they developed is not used for COVID-19 immunization, it can be adapted for other viral threats in the future, using the same viral nanoparticles and drug delivery methods combined with a different antigen.
Photo: A 3D rendering of the stucture of the cowpea mosaic virus. This plant virus is one of two viruses UC-San Diego researchers used to create new thermally stable COVID-19 vaccine candidates. Credit: Thomas Splettstoesser, Wikimedia Commons, CC BY-SA 3.0, image resized from original.