Source: Trinity College Dublin

Immunologists from Trinity College in Dublin say they have unearthed a key piece of the MRSA vaccine puzzle by identifying specific T-helper cells whose role in the immune response is critical in affecting infection outcomes. The researchers were able to develop a model vaccine, which targeted T-helper type 1 cells, and then showed experimentally that its use led to improved infection outcomes.

“To design an effective vaccine, it is imperative you know how a bacterium interacts with its host,” said Rachel McLoughlin, Ph.D., assistant professor in immunology. “By screening patients with Staphylococcus aureus bloodstream infections, we were able to isolate key players in the immune system that dealt with these infections. And then we designed a model vaccine that effectively sparked them into action.”

The World Health Organization warns of an impending post-antibiotic era, with the potential to undermine modern medicine. Antimicrobial resistance is a global crisis that demands the development of new antimicrobials, but developing alternatives to antibiotics such as vaccines would prevent infection in the first place.

The bacterium S. aureus is a major cause of healthcare-associated infections, and bloodstream infections caused by S. aureus are associated with significant mortality. Resistance in S. aureus to the main antibiotic used for treatment, methicillin, was first reported in the 1960s, and over the past decades, antibiotic resistant S. aureus, or MRSA, has become endemic in hospitals throughout the world.

To date, around eight promising candidate vaccines have failed in clinical trials despite showing promise in preclinical models. Traditional approaches to vaccine development have thus failed to develop an effective weapon against MRSA.

Scientists now know that cellular immunity (involving T cells) is vitally important in protection against S. aureus infection, because individual T-cell subsets are very important for activating phagocytes, the immune cells that ingest and kill bacteria.

Dr. McLoughlin and her colleagues found that T-helper type 1 cells were elevated in patients following S. aureus infection. Their model vaccine, which jolted these cells into action, improved infection outcomes. The results therefore support the design of vaccines that specifically target these cells in humans.

“This study demonstrates the importance of truly translational research,” commented Dr. McLoughlin. “Using preclinical models, we identified an immune mechanism important for protection against S. aureus infection, but it was via collaboration with clinicians at three Dublin teaching hospitals that we were able to translate these findings to show the same mechanism of immunity is relevant in human infection. Our findings will directly inform the design of next-generation anti-S. aureus vaccines and could significantly increase our chances of realizing an effective vaccine to protect patients from MRSA.”