image: Removing the glycans (dark blue on the left illustration) from a coronavirus’ spike protein leads to greater vaccine efficacy.
Credit: Lorenzo Casalino
SAN DIEGO, March 25, 2025 — Sugar coatings aren’t only for candies; they also help viruses, like the ones that cause COVID-19, hide from their hosts’ immune system. Now, researchers have developed a universal vaccine that targets coronaviruses and the sugars that they use as cover. As demonstrated in animal studies, the vaccine removed sugar molecules from an area of a coronavirus spike protein that rarely mutates and created effective and plentiful antibodies to inactivate the virus.
Chi-Huey Wong, a chemistry professor at Scripps Research, will present results from his team’s studies today at the ACS Spring 2025 Digital Meeting, a meeting of the American Chemical Society.
Wong says that the premise of this research is simple: It’s an effective vaccine that targets more than one coronavirus at a time, which will allow individuals to receive a single shot for protection against multiple infectious agents. An ongoing Phase I clinical trial led by Rock Biotherapeutics has completed enrollment and dosing and will be discussed by Wong during his ACS Spring 2025 Digital Meeting presentation.
“For a lot of vaccines, like smallpox and tetanus, we only have to be immunized once,” Wong says. “But we have to take a flu shot every year.” He adds that the high rate of mutation seen in the SARS-CoV-2 virus — specifically, the receptor binding domain on the virus’ spike protein — has led to an unprecedented number of COVID-19 vaccine updates.
The low-mutation region that Wong’s team chose to target for the new vaccine is within the stalk region of the virus’ spike protein. However, this stalk is coated with chains of sugar molecules called glycans from the host’s cells. And the sugar coating keeps antibodies from recognizing, and therefore inactivating, the virus.
So, the researchers devised a “low-sugar” vaccine that removes the protective glycans through enzymatic digestion and creates antibodies that specifically target the low-mutation stalk region of the virus’ spike protein, should the actual virus enter the body.
In animal studies with hamsters and mice, the universal vaccine created more diverse antibodies with higher titers (concentrations in the blood, where immune system cells travel throughout the body) compared to individual vaccines against variants of SARS-CoV, as well as MERS-CoV, the virus that causes Middle East respiratory syndrome. This improved and broadened the vaccine’s protection. Wong says the team’s new vaccine could also provide protection against coronaviruses that cause influenza and the common cold.
In addition to vaccines for viral infections, Wong’s team is using the technique to develop vaccines for the treatment of various cancers. They recently published two studies on glycan targets on cancer cells and enzymes linked to the synthesis of glycans on cancer cells in the Journal of the American Chemical Society.
This research was funded by Academia Sinica.
Visit the ACS Spring 2025 program to learn more about this presentation, “Development of low-sugar universal vaccines and glycoengineered antibodies with improved Fc-mediated killing” and other science presentations.
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Title
Development of low-sugar universal vaccines and glycoengineered antibodies with improved Fc-mediated killing
Abstract
Chi-Huey Wong
Department of Chemistry, The Scripps Research Institute, La Jolla, CA 92037
Glycosylation is an important reaction used to modulate the structure and function of biomolecules in living organisms. Most human viruses, for example, depend on the host glycosylation machinery to create a sugar coat on the virus to complete their life cycle. We found that the main immunogens of influenza and COVID viruses are highly glycosylated, particularly in the conserved epitopes, to facilitate infection and escape from immune response. We also found that deletion of the sugar coat to expose the highly conserved epitopes elicited broadly protective antibody and T cell responses against the virus and different variants. In addition, the antibodies induced by such low-sugar vaccines are more diverse with higher titers against the immunogen, especially the highly conserved epitopes, thus broadening the scope of protection. Furthermore, the Fc-glycans on the antibody can be engineered to improve antibody-mediated killing. This lecture will present our recent development of broadly protective low-sugar vaccines and glycoengineered antibodies with improved Fc-mediated killing.