Viruses like SARS-CoV-2 use sugar molecules to evade the immune system, but Scripps Research scientists have designed a universal coronavirus vaccine that removes these sugars and exposes a stable, rarely mutated part of the spike protein. The approach triggered strong immune responses in animal studies and showed promise in neutralizing a variety of coronaviruses, including those that causeCOVID-19, MERS and even common cold coronaviruses.

Removing glycans from the coronavirus spike protein (dark blue in the image at left) could increase vaccine effectiveness. Photo credit: LorenzoCasalino

Viruses, including the one that causes COVID-19, use sugar molecules on their surface to hide from the immune system, acting like a protective coating. Now, researchers have developed a universal coronavirus vaccine that targets both the virus and the sugar they use to avoid detection. In animal studies, the vaccine removed these sugar molecules from stable regions of the coronavirus spike protein, helping the immune system produce powerful and effective antibodies to neutralize the virus.

Chi-Huey Wong, professor of chemistry at Scripps Research, presented his team’s research results at the ACS 2025 Spring Digital Meeting hosted by the American Chemical Society.

The goal, Wong explained, is to develop a vaccine that protects against multiple coronaviruses, thereby reducing the need for frequent booster shots. The Phase I clinical trial led by Rock Biotherapeutics has completed recruitment and dosing. Wong's presentation will also highlight the results of the trial.

"For many vaccines, such as smallpox and tetanus, we only need one dose," Huang said. "But we have to get the flu vaccine every year." He added that the high mutation rate of the SARS-CoV-2 virus (specifically, the receptor-binding domain on the virus's spike protein) has led to an unprecedented number of COVID-19 vaccine updates.

The low-mutation region chosen by Huang's team for the new vaccine is located within the stem region of the virus's spike protein. However, this stem is wrapped in chains of sugar molecules called glycans from the host cell. Sugar coating makes it impossible for antibodies to recognize and inactivate the virus.

So the researchers designed a "low-sugar" vaccine that removes protective glycans through enzymatic digestion and produces antibodies that specifically target the low-mutated stem of the virus's spike protein if the virus actually enters the body.

In animal studies in hamsters and mice, the universal vaccine produced more diverse and higher titers of antibodies (concentrations in the blood, where immune system cells spread throughout the body) than individual vaccines targeting SARS-CoV variants as well as MERS-CoV, the virus that causes Middle East respiratory syndrome. This improves and expands the scope of protection of the vaccine. Huang said 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, Professor Huang's team is also using this technology to develop vaccines to treat various cancers. They recently published two studies in the Journal of the American Chemical Society on glycan targets on cancer cells and enzymes involved in glycan synthesis on cancer cells.

Compiled from /ScitechDaily