Viruses like SARS-CoV-2 use sugar molecules to hide from the immune system, but scientists at Scripps Research have designed a universal coronavirus vaccine that strips these sugars and exposes a stable, rarely mutating part of the spike protein.
This approach triggered strong immune responses in animal studies and showed promise in neutralizing multiple coronaviruses, including those causing COVID-19, MERS, and even the common cold.
A Sweet Shield: How Viruses Use Sugars to Hide
Viruses, including those that cause COVID-19, use sugar molecules on their surfaces to hide from the immune system, much like a protective coating. Now, researchers have developed a universal coronavirus vaccine that targets both the viruses and the sugars they use to avoid detection. In animal studies, the vaccine removed these sugar molecules from a stable region of the coronavirus spike protein, helping the immune system produce strong and effective antibodies to neutralize the virus.
Chi-Huey Wong, a chemistry professor at Scripps Research, is presenting his team’s findings at the ACS Spring 2025 Digital Meeting, hosted by the American Chemical Society.
One Shot, Many Protections
Wong explains that the goal is to create a single vaccine that protects against multiple coronaviruses, potentially reducing the need for frequent boosters. A Phase I clinical trial, led by Rock Biotherapeutics, has already completed enrollment and dosing. The results of this trial will also be highlighted in Wong’s 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.
Targeting the Virus’ Low-Mutation Core
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.
Animal Tests Show Broad Protection
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.
Cancer Vaccines May Be Next
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.
Meeting: ACS Spring 2025
Title
Development of low-sugar universal vaccines and glycoengineered antibodies with improved Fc-mediated killing
Abstract
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.
This research was funded by Academia Sinica.
