By combining four proteins of Staphylococcus aureus that individually generated the strongest immune response in mice, scientists have created a vaccine that significantly protects the animals from diverse strains of the bacterium that cause disease in humans. A report describing the University of Chicago study, funded by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health, appears online this week in the Proceedings of the National Academy of Sciences.
?This finding represents a promising step toward identifying potential components to combine into a vaccine designed for people at high risk of invasive S. aureus infection,? notes Anthony S. Fauci, M.D., NIAID director.
S. aureus, the most common agent of hospital-acquired infection, is the leading cause of bloodstream, lower respiratory tract and skin infections. These infections can result in a variety of illnesses, including endocarditis (inflammation of the heart), toxic-shock syndrome and food poisoning.
Research in S. aureus has taken on new urgency: In the past few decades, the bacterium has developed resistance to traditional antibiotics, thus allowing infections to spread throughout the body of the infected individual despite treatment. More recently, healthy people with no apparent risk factors have been infected by novel and extremely virulent strains of S. aureus acquired from community rather than hospital sources.
Olaf Schneewind, M.D., Ph.D., led the University of Chicago research group. Using available genome sequencing and analysis of antigenic proteins from diverse S. aureus strains, the researchers tested 19 surface proteins to see if they triggered an immune response in mice. The group then identified four individual proteins ? IsdA, IsdB, SdrD and SdrE ? that provided the strongest immune response, combined them into a vaccine and tested the combination vaccine in mice.
?When we challenged the immunized mice by exposing them to a human strain of S. aureus, the combination vaccine provided complete protection, whereas the control group developed bacterial abscesses,? says Dr. Schneewind. For comparative purposes, the researchers also tested all four proteins as individual vaccines. These vaccines provided either no protection or modest protection, says Dr. Schneewind.
The researchers then tested the combination vaccine in mice again, this time challenging groups of 10 vaccinated mice for seven days using five different S. aureus strains that infect humans. The vaccine offered significant protection against all strains examined.
Dr. Schneewind and his colleagues are now exploring the relationship between antibodies that fight S. aureus infection and surface proteins of the bacterium that facilitate the spread of the infection.