(Skeeze, Pixabay)
24 Mar. 2021. Researchers at two Virginia universities developed an experimental vaccine that in tests with pigs protects against SARS-CoV-2 and other coronaviruses. A team from University of Virginia in Charlottesville and Virginia Tech in Blacksburg describe the vaccine and tests in a non-peer reviewed paper posted last week on the bioRxiv server.
The researchers led by UVa medical school professor of pediatrics Steven Zeichner and VaTech veterinary medicine professor Xiang-Jin Meng are seeking a vaccine that can protect against disease from currently known SARS-CoV-2 strains responsible for Covid-19 infections, but also other mutations in SARS-CoV-2 and coronaviruses yet unknown. A broadly protective vaccine of this kind could help protect populations against future coronavirus pandemics arising from zoonotic viruses that jump from animals to humans.
Zeichner and Meng created their vaccine using genetically altered E. coli bacteria. While popularly associated with food poisoning, E. coli appears in many non-toxic varieties and is a widely studied model for research on microorganisms. The researchers deleted a large part of the genome from an E. coli strain that removed the bacterium’s outer surface, making it more susceptible and responsive to viruses. The team then inserted a synthetic form of circular DNA called a plasmid in the E. coli, with genetic code instructions to populate the surface of the modified E. coli with antigen proteins for a vaccine.
Those antigen proteins, designed in the plasmid’s genetic code as a fusion peptide, combine 13 amino acids that address common regions of the spike protein found on many types of coronaviruses, including those that infect animals as well as humans. From that modified E. coli platform, the researchers produced a vaccine designed to protect against the SARS-CoV-2 virus and porcine epidemic diarrhea virus or PEDV, a life-threatening coronavirus disease affecting pigs, causing diarrhea, vomiting, and dehydration. The two coronaviruses are distant relatives, but have similar spike protein chemistries.
One vaccine protects against two diseases
The UVa/VaTech team tested both vaccines on pigs, since pigs have organs similar in size and function as humans. After injecting the vaccine, the researchers injected the pigs with SARS-CoV-2 and PEDV viruses to test the vaccines’ protective responses. The results showed each vaccine produced antibodies against its specific disease target, including production of IFN-gamma cytokine enzymes indicating a strong immune response. And while each vaccine did not protect against infection, the vaccines did reduce viral loads and prevent disease symptoms from occurring.
In an another important finding, the SARS-CoV-2 vaccine also protected pigs against PEDV. For example, the SARS-CoV-2 vaccine reduced PEDV viral loads in jejunum tissue found in the pigs’ small intestines. As a result, the researchers believe this technology can be the basis for a broadly protective vaccine against a variety of coronaviruses.
Key features of the E. coli bacterial platform are its plug-and-play design and low cost of manufacturing. Researchers say they need only two or three weeks to produce new antigen proteins for a vaccine from the modified E. coli, once the target sequence is identified. And the team produced vaccines for this study using fermentation, a common inexpensive process for making vaccines against cholera and whooping cough, particularly in low-resource regions.
“Factories in many low-to-middle-income countries around the world are making hundreds of millions of doses of those vaccines per year now, for a $1 per dose or less,” says Zeichner in a UVa statement. “It may be possible to adapt those factories to make this new vaccine. Since the technology is very similar, the cost should be similar too.”
UVa and VaTech filed a provisional patent on the vaccine technology. The researchers say more preclinical tests and clinical trials are needed to determine the vaccine’s safety and efficacy before seeking regulatory authorization.
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