Research from the Penn State College of Medicine has brought us one step closer to a vaccine design strategy that could guard against new variations of SARS-CoV-2, the virus that causes COVID-19, as well as possibly protect against other coronaviruses. To create proteins called immunogens that can trigger an immune response, the researchers engineered portions of the SARS-CoV-2 virus that are less prone to mutation.
The surface spike protein of SARS-CoV-2, a primary target of antibodies, interacts with the angiotensin-converting enzyme 2 receptors to allow the virus to enter host cells. The receptor binding domain (RBD) of the spike protein is the focus of existing vaccines, but RBD mutation susceptibility allows viruses to evade neutralizing antibodies.
The researchers published a paper on the structure and performance of their immunogens, which target the virus differently, just a few weeks after the Centers for Disease Control and Prevention authorized a new bivalent COVID-19 vaccine. These immunogens, as opposed to currently available vaccines, are created using conserved sections of the spike protein that are less prone to mutation.
To create the immunogens, the scientists used computational biology to pinpoint three areas of the spike protein that have remained constant after millions of potential changes. These regions, known as epitopes, were matched and grafted to protein scaffolds, which gave the epitopes stability in solutions. After that, the immunogens’ structural performance was improved through a variety of design changes, including stabilizing mutations. The stability of the immunogens was tested using computer simulations. Earlier, Dokholyan described this computational biology strategy.
The scientists employed computational biology to identify three regions of the spike protein that have remained constant following millions of potential alterations. These regions were then used to produce the immunogens. These areas, called epitopes, were matched to protein scaffolds and grafted onto them, giving the epitopes stability in solutions. Following that, the structural performance of the immunogens was enhanced through a range of design modifications, including stabilizing mutations. Using computer models, the immunogens’ stability was examined. Dokholyan already explained this computational biology method.
The scientists produced the genetically engineered immunogens using the recombinant expression method, which involves giving bacteria the instructions they need to produce proteins. Following purification, the proteins were examined in the lab to make sure they were almost identical to their computer-generated counterparts. Finally, the scientists created four stable immunogen designs that were utilized to immunize mice, which caused them to manufacture antibodies against SARS-CoV-2. Diverse levels of antibodies were produced by each design, but ED2 exhibited a strong immune response.
The SARS-CoV-2 spike protein was discovered by the researchers to be linked to these antibodies during additional testing. Using specialized chemical tests they developed, scientists also assessed how strongly the ED2 immunogen bonded to serum samples from human COVID-19 patients. They discovered that the serum samples from COVID-19 patients’ antibodies could bind to the ED2 immunogens, indicating that they might also be employed for diagnostic purposes. On October 3, the approach and findings were released in the journal Advanced Functional Materials.
Researchers say that additional research will be conducted to improve the immunogens’ design and immunological response. They could eventually be tested in clinical trials as vaccine candidates once they are refined.
According to Vishweshwaraiah, Our methodology could be applied not only for SARS-CoV-2 and other related viruses but also for other clinically relevant pathogenic viruses. We are the first, as far as we are aware, to create immunogens based on conserved sections of the SARS-CoV-2 spike protein. The developed immunogens have produced encouraging results, and we intend to further enhance them.