COVID-19 Vaccine Innovation Could Dramatically Accelerate World Production

Science on July 23, 2020. Six key modifications, called proline, are indicated as red and blue spheres and help block the protein in the prefusion conformation, the form it takes before infection. Credit: University of Texas at Austin. “Width =” 800 “height =” 480 “/>

Responding to the need to rapidly develop billions of doses of life-saving COVID-19 vaccines, a scientific team at the University of Texas at Austin has successfully redesigned a key coronavirus protein, and the modification could allow for vaccine production much faster and more stable worldwide.

The new findings are described in the journal. Science.

Most coronavirus vaccine candidates train the human immune system to recognize a key protein on the surface of the SARS-CoV-2 virus called the spike protein to fight infection. The researchers designed a new version of this protein that, when expressed in cells, produces up to 10 times more protein than that of a previous synthetic peak protein that was already in use in multiple COVID-19 vaccines. Along with colleagues from the National Institutes of Health, several members of the UT research team also designed the previous version of the spike protein found in at least two COVID-19 vaccine candidates currently in clinical trials in the United States.

“Depending on the type of vaccine, this improved version of the protein could reduce the size of each dose or speed up vaccine production,” said Jason McLellan, associate professor in the Department of Molecular Biosciences and lead author of the paper. “Either way, it could mean that more patients have access to vaccines faster.”

Dubbed HexaPro, the new protein is also more stable than the team’s previous version of the spike protein, which should make it easier to store and transport. It also maintains its shape even under heat stress, during storage at room temperature and through multiple freezes and thaws. Such qualities are desirable in a robust vaccine.

The Bill & Melinda Gates Foundation has contributed to the development of technology through a grant in the interest of making vaccines accessible to people in low-income countries. Vaccine companies with different platform technologies will have the ability to further test and develop COVID vaccines that use HexaPro. McLellan has also indicated that the partners have an interest in extending access to technology to people in the developing world.

“Four billion people living in developing countries will need access to a vaccine, like all of us,” said McLellan.

HexaPro could also be used in COVID-19 antibody tests where it would act as a probe to identify the presence of antibodies in a patient’s blood, indicating whether a person has previously been infected with the virus.

The paper’s first author is Ching-Lin Hsieh, a postdoctoral researcher in McLellan’s lab. The corresponding authors are McLellan; Ilya Finkelstein, associate professor in the Department of Molecular Biosciences; and Jennifer Maynard, professor at the Cockrell School of Engineering.

The team’s original version of the spike protein forms the basis of vaccine candidates currently in human clinical trials, including Moderna mRNA-1273 and NVX-CoV2373 from Novavax.

For nucleic acid-based vaccines that use the patient’s own cells to create the viral proteins that trigger an immune response, such as mRNA-1273, this improved spike protein could allow next-generation versions that require a much lower dose to produce the same immunity. response from a patient. For subunit vaccines that contain a version of the actual viral protein as an antigen, such as NVX-CoV2373, many more doses of vaccine could be produced in the same time period. Either way, from a production standpoint, this could mean accelerating access to life-saving vaccines.

Building on their experience in creating stabilized proteins such as vaccines against MERS-CoV, the coronavirus that causes Middle East respiratory syndrome, and other viruses, the researchers identified 100 different modifications to the spike protein that they believed could lead to a more stable and highly expressed expression. version. They then created 100 different versions of the protein by inserting the gene blueprints for each version into a different culture of human cells. Of those 100 versions of the spike protein, 26 were more stable or had higher expression.

The researchers then took four of those beneficial modifications, plus two of their original stabilized peak protein, and combined them to create HexaPro. When they inserted the gene blueprints for this version of the spike protein into a human cell culture, the cells produced 10 times more protein than their original protein.