) bacteria, is the leading cause of potentially dangerous skin infections, are most feared for the drug-resistant strains that have become a serious threat to public health. Attempts to develop a vaccine
against methicillin-resistant Staphylococcus aureus
(MRSA) have failed to outsmart the superbug's ubiquity and adaptability to antibiotics.
However a new study from Washington University School of Medicine in St. Louis may help explain why previous attempts to develop a staph vaccine
have failed, while also suggesting a new approach to vaccine
design. This approach focuses on activating an untapped set of immune cells, as well as immunizing against staph in utero or within the first few days after birth.
The new research, in mice, found that T cells, one of the body's major types of highly specific immune cells, play a critical role in protecting against staph
bacteria. Most vaccines
rely solely on stimulating the other main type of immune cells, the B cells, which produce antibodies to attack disease-causing microorganisms such as bacteria.
The study findings are published in the Journal of Clinical Investigation
Senior author Dr Juliane Bubeck Wardenburg, MD, Ph.D., director of the university's Division of Pediatric Critical Care told Thailand Medical
news, "Across the globe, staph
infections have become a pervasive health threat because of increasing antibiotic resistance. Despite the medical community's best efforts, the superbug has shown a consistent ability to elude treatment. Our findings indicate that a robust T cell response is absolutely essential for protection against staph
Dangerous and highly contagious, staph
survives and thrives on human skin and can be spread through skin-to-skin contact or exposure via contaminated surfaces. Generally, the bacteria live harmlessly and invisibly in about one-third of the population. From their residence on the skin, the bacteria can cause red, pus-filled sores. Ever persistent, the superbug will deliver recurrent infections in about half of its victims.
strains can enter the bloodstream, bones or organs and lead to pneumonia, severe organ damage and other serious complications in hundreds of thousands of people each year. More than 10,000 people die in the U.S. from drug-resistant staph
Dr Bubeck Wardenburg added, "The focus in the vaccine
field for Staphylococcus aureus
during the past 20 years has been on generating antibody responses, not on specific T cell responses. This new approach shows promise."
For more than 15 years, Dr Bubeck Wardenburg has studied a single toxin called alpha-toxin
strong>, made by staph. This toxin plays a role in tissue damage in multiple forms of infection. "An important thing about the alpha-toxin is that it is found in all staph strains, meaning those that are and are not antibiotic-resistant," she said. "Understanding this allowed us to devise studies in mice that examined the effect of alpha-toxin on the immune response in minor skin infections as well as in more serious infections that spread in the bloodstream."
The medical researchers found that the immune cells did not protect mice that had minor staph infections on their skin.
However, mice that were exposed to life-threatening staph infections in the bloodstream did develop protection.
"We discovered a robust T cell response targeting staph in the bloodstream," Dr Bubeck Wardenburg said. "By contrast, T cells were diminished in skin infections as a result of the toxin. Because skin infection is very common, we think that staph uses alpha-toxin to prevent the body from activating a T cell response that affords protection against the bacteria."
From a macro perspective, Dr Bubeck Wardenburg said blocking the toxin in skin infections may yield a healthy T cell response.
In addition, protecting the T cell response from the time of birth may reprogram the bacteria's overall effect on the immune system. "This bug is deliberate and acts in a sinister way early on," she said. "The bug appears to be using the toxin to shape the T cell response in a way that's favorable for the bug but not for humans."
Past vaccine development efforts have focused on adults. However, Bubeck Wardenburg said, a vaccine may be more likely to succeed if administered before infants first encounter staph. Therefore, immunization should happen before initial exposure to staph, to block the toxin and generate a vigorous T cell response.
Dr Bubeck Wardenburg further added, "We envision two strategies. One is immunizing pregnant women so they can transfer antibodies that protect infants against the toxin at birth. The second involves immunizing infants within a day or two after birth. Neither of these strategies has been considered for staph vaccines to date.
Reference: Staphylococcus aureus α-toxin suppresses antigen-specific T cell responses
Brandon Lee, Reuben Olaniyi, Jakub Kwiecinski, and Juliane Bubeck Wardenburg
Published December 24, 2019
Citation Information: J Clin Invest. 2019. https://doi.org/10.1172/JCI130728.