The misuse of antimicrobials is leading to an alarming increase in antimicrobial-resistant infections, with the World Health Organization estimating that over 1 million deaths occurred worldwide in 2019. The concern is that in the next 20 to 30 years, many of our current drugs may become ineffective, bringing us back to the pre-antibiotic era. Xuefei Huang, a Michigan State University Research Foundation Professor in the Departments of Chemistry and Biomedical Engineering, emphasizes the urgency of the situation.

To combat this global threat, Huang and his team have made a significant breakthrough in a Nature Communications study. They have developed a promising vaccine candidate for antibiotic-resistant bacteria, specifically for Staphylococcus aureus and its methicillin-resistant counterpart, MRSA. These bacteria are among the most common causes of bacterial infections.

Using an innovative delivery platform created by Huang’s group at MSU, the team’s preclinical vaccine formulation showed high levels of immunity against lethal levels of staph and MRSA in animal trials. This advancement expands the boundaries of vaccine science, providing valuable insights for researchers to enhance and refine future bacterial vaccines.

To create a vaccine, researchers must first identify an effective antigen. This is a substance or molecule that the body recognizes as foreign, triggering an immune response and the production of antibodies to fight future infections. While most vaccines rely on protein antigens, Huang specializes in the chemistry and biology of carbohydrates.

Carbohydrates, composed of saccharides or sugars, offer unique challenges and advantages as antigens in vaccines. Sugar structures are specific to certain bacteria, meaning a vaccine effective against one bacterium may not work against another, even if they are similar. This is why a single dose of a bacterial vaccine may contain multiple antigens, such as the 20 unique strains protected against in Pfizer’s PREVNAR 20 pediatric pneumonia vaccine.

If researchers can develop a shared antigen among many—if not all—bacteria, vaccination coverage would be significantly improved. Gerald Pier, a professor of medicine at Harvard Medical School and Brigham and Women’s Hospital 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, as well as many other bacteria and even fungi. Its prevalence makes it an attractive candidate, offering potential protection against a wide range of pathogens. By examining PNAG as an antigen candidate for staph, Pier, Huang, and their colleagues are unraveling the secrets needed to create a more effective vaccine.