MSU Research Foundation Professor Leads Development of Vaccine to Combat Antibiotic Resistance

Michigan State University Professor Xuefei Huang and his team have developed a new vaccine candidate to combat antibiotic-resistant bacteria, potentially improving the fight against deadly infections.

Michigan State University Professor Xuefei Huang. Courtesy image.

Driven by the overuse of antimicrobials, pathogens are quickly building up resistances to once-successful treatments. It’s estimated that antimicrobial-resistant infections killed more than 1 million people worldwide in 2019, according to the World Health Organization.

“There are worries that at the rate things are going, in perhaps 20 or 30 years, few of our drugs will be effective at all,” said Xuefei Huang, a Michigan State University Research Foundation Professor in the departments of Chemistry and Biomedical Engineering. “This would bring us back to the pre-antibiotic age.”

In a new Nature Communications study, Huang and his collaborators have reported a breakthrough that will help tackle this global threat head-on. Specifically, the team has created a promising vaccine candidate for antibiotic-resistant bacteria. Bacterial vaccines, along with antibiotics, are a crucial tool in the fight against deadly microbes. In the latest paper, Huang announced several discoveries that will help the development of a carbohydrate-based vaccine for infections caused by Staphylococcus aureus and its “superbug” relative methicillin-resistant Staphylococcus aureus, or MRSA.

Using an innovative delivery platform created by the Huang group at MSU, the team’s preclinical vaccine formulation offered high levels of immunity from lethal levels of staph and MRSA in animal trials. With this work, Huang and his team have expanded the frontiers of vaccine science, equipping fellow researchers with new knowledge to improve and refine future bacterial vaccines.

To develop a vaccine, researchers must identify an effective antigen. While most vaccines rely on protein antigens, Huang is an expert in the chemistry and biology of carbohydrates. Developing carbohydrates to use as antigens in vaccines comes with its own unique challenges and advantages.

“Sugar structures are very specific to certain bacteria,” Huang explained. “A vaccine that works against one bacterium might not work at all against another, even if they’re very similar.” This is why a single dose of a bacterial vaccine can contain many different antigens.

If researchers can develop an antigen that’s shared among many — if not all — bacteria, vaccination coverage would be greatly improved.

Gerald Pier, professor of medicine at Harvard Medical School and a collaborator on the latest MSU-led paper, has studied one such antigen candidate for years. Polysaccharide poly-β-(1−6)-N-acetylglucosamine, or PNAG, is a carbohydrate found on the cell wall of staph, many other bacteria, and even fungi. This prevalence makes it extremely useful, offering potential protection against numerous pathogens at once.

By examining PNAG as an antigen candidate for staph, Pier, Huang and their colleagues are unlocking the secrets needed to make a more effective vaccine.

Huang’s team created a library of 32 different PNAG structures. By screening these 32 structures with antibody studies, they discovered that the fine pattern of PNAG matters significantly. The team identified two PNAG combinations that were especially promising and attached them to a groundbreaking vaccine delivery platform based on a bacteriophage called Qbeta. This modified bacteriophage, mQβ (pronounced "cue beta"), helps create an enhanced immune reaction.

When coupled with mQβ, the two most promising PNAG pentasaccharides offered high levels of protection in mice against staph and MRSA. The team's new vaccine construct outperformed another PNAG-vaccine delivery system currently in human trials. This advancement is crucial in the fight against antibiotic resistance, potentially reducing the need for antibiotics and preventing the emergence of resistant strains.

The breakthrough delivery platform earned Huang the 2024 Technology Transfer Achievement Award.

Xuefei Huang is a MSU Research Foundation Professor, a title is granted to highly accomplished current or incoming faculty members recommended by their college or dean. These distinguished researchers excel in their fields, furthering scholarly, disciplinary, or research areas crucial to MSU. Recipients retain the title throughout their tenure and typically receive scholarly support for the first five years after recognition. More than 60 professors have been honored with the MSU Research Foundation Professor title.

Read the full article at MSU College of Natural Science Department of Chemistry