Study: Plant-, Bacteria-based Vaccines Unaffected by COVID-19 Mutations

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Nanoengineers at the University of California San Diego have developed a COVID-19 vaccine that solves a trifecta of current issues: 1) it is stable at high temperatures and 2) it is seemingly unaffected by mutations, therefore bringing about the possibility of a future 3) pan-coronavirus vaccine.

The new refrigerator-free COVID-19 vaccines are still in the early stages of development; but, in mice, the candidates triggered a high production of neutralizing antibodies against SARS-CoV-2. One of the tested vaccines is made from a plant virus, called cowpea mosaic virus, while the other is made from a bacteriophage, called Q beta.

According to the researchers’ paper, published in the Journal of the American Chemical Society, they used cowpea plants and E. coli to grow copies of the plant virus and bacteriophage in the form of ball-shaped nanoparticles. They then harvested the nanoparticles and attached a small piece of the SARS-CoV-2 Spike protein to the surface.

As with current COVID-19 vaccines, the Spike protein is what stimulated the mouse immune system to generate a response against SARS-CoV-2. The difference in this vaccine, however, lies in the specific piece of the Spike protein that the researchers exploited. One of the pieces chosen, called an epitope, is almost identical between SARS-CoV-2 and the original SARS virus.

“The fact that neutralization is so profound with an epitope that’s so well conserved among another deadly coronavirus is remarkable,” said study co-author Matthew Shin, a nanoengineering Ph.D. student in the Steinmetz Lab at UCSD. “This gives us hope for a potential pan-coronavirus vaccine that could offer protection against future pandemics.”

Another huge advantage of the team’s chosen epitope is that it does not seem to be affected by any of the SARS-CoV-2 mutations that have been reported thus far. The researchers say that’s because this epitope comes from a region of the Spike protein that does not directly bind to cells—another difference between this vaccine and currently administered COVID-19 vaccines. Vaccines like Pfizer and Moderna’s leverage epitopes from the Spike protein’s binding region, where several mutations—including the Delta variant—have occurred.

Additionally, the fact that the plant virus and bacteriophage nanoparticles are stable at high temperatures is yet another benefit of the developing vaccine—and another asset that sets it apart from current versions. The cold storage-free vaccines could be a big game changer for global distribution efforts, including those in rural areas, resource-poor communities and other areas that lack healthcare infrastructure.

The vaccines still have a long way to go before making it to clinical trials. But, even if they end up ineffective against COVID-19, the research team says the technology can be quickly adapted for the next virus threat.

Study author Nicole Steinmetz describes the vaccine technology as “plug and play.”

“We use the same nanoparticles, the same polymers, the same equipment, and the same chemistry to put everything together. The only variable, really, is the antigen that we stick to the surface,” said Steinmetz, who is the director of the Center for Nano-ImmunoEngineering at UCSD.

In fact, Steinmetz has used this recipe in previous studies to develop vaccine candidates for disease like HPV and cholesterol.

Next, the research team will conduct in vivo testing to confirm the two vaccine candidates protect against COVID-19 and its variants, including Delta, as well as other known coronaviruses.

 

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