James B. Dale, MD, Gene H. Stollerman Professor of Medicine and chief of the Division of Infectious Diseases at the University of Tennessee Health Science Center (UTHSC), recently received a $3,942,923 grant from the National Institute of Allergy and Infectious Diseases, a branch of the National Institutes of Health (NIH), for his project titled “Structure-Based Design of a Broadly Protective Group A Streptococcal Vaccine.” The funding will be used to develop a safe, broadly effective, and affordable vaccine to prevent Group A streptococcal (GAS) infections, most commonly known as strep throat, and their complications.
Group A streptococcal infections can range from a mild skin infection or a sore throat, to severe, invasive infections such as toxic shock syndrome, bacteremia (bloodstream infection), and pneumonia. In some cases, individuals with GAS infections may develop glomerulonephritis (acute inflammation of the kidney), rheumatic fever, or rheumatic heart disease. These more serious diseases can lead to significant morbidity and mortality, especially in underdeveloped countries and impoverished pockets of developed nations.
Dr. Dale, together with a University of Tennessee lab in Knoxville and researchers at Oak Ridge National Laboratory, are developing an entirely new approach to GAS vaccine design and development. Ultimately aiming to tackle the global morbidity and mortality caused by Group A streptococcal invasive infections and their complications, Dr. Dale and his team are using the new funding to develop a universal vaccine that could have a major impact on the health of millions of people worldwide.
“Immunity is classically described as ‘type-specific,’ implying that natural immunity protects against only one of the more than 200 different M protein types of group A streptococci,” Dr. Dale said. “Through our research, we’ve found that there is a need for a paradigm shift away from the concept of ‘type-specific’ immunity against GAS infections to one of ‘cluster specific’ immunity.”
Dr. Dale hypothesizes that immunity to GAS infections is the result of both type-specific and cross-protective antibodies. He further proposes that a new approach employing computational predictions of peptide structures will result in the development of a multivalent vaccine leading to broadly protective immunity in populations around the world.
“Using the most modern computational tools, we are defining the relationships among these different proteins so that we can select the fewest number of protein fragments to put in a structure-based vaccine that will represent as many different types of strep as possible,” Dr. Dale said. “This newly developed universal vaccine would be deployed throughout the world and be more effective than any ever developed before if successful.”
Preliminary data provides an optimistic outlook on the new structure-based vaccine, according to Dr. Dale. Even a partially effective vaccine would have “a significant impact on global health,” he said.
This project is a continuation of over 30 years of ongoing research done by Dr. Dale, who has been with UTHSC since the 1980s, and his team. The project is slated to continue through 2022.