UTHSC researcher developing vaccine to help eradicate rheumatic heart disease, saving thousands of lives each year.
Anyone who has spent time around children is likely familiar with strep throat, a common bacterial infection treated with antibiotics in high-income countries. However, in low-to-moderate-income parts of the world, this seemingly innocuous infection can become deadly due to a lack of comprehensive access to healthcare.
The bacterium that causes strep throat is group A streptococcus (GAS). Without treatment, GAS can develop into more serious infections, such as streptococcal toxic shock, necrotizing fasciitis (“flesh-eating disease”), or pneumonia, among others. In addition, some infections may trigger autoimmune-mediated acute rheumatic fever (ARF), leading to rheumatic heart disease (RHD). According to the World Health Organization, around 30 million people suffer from RHD. In 2015 alone, the disease was responsible for over 300,000 deaths and over 11 million individuals reported dealing with an RHD-related disability.
James (Jim) Dale, the Gene H. Stollerman Professor of Medicine and Chief of the Division of Infectious Diseases at the University of Tennessee Health Science Center, has dedicated a large part of his 36-year career to designing, developing and clinically testing streptococcal vaccines. He is internationally known for his GAS research and has been developing StreptAnova, a multivalent GAS vaccine, since the early 2010s.
“The push in my lab and with my research group for the last 10 to 15 years has focused on vaccine development,” said Dale. “Can we develop a vaccine that will prevent the infections that trigger rheumatic fever and RHD and save lives? That’s the overall goal.”
There are over 200 M (emm) protein types of GAS bacteria around the world. StreptAnova is a novel, complicated vaccine because it must provide immunity for a large range of these types of bacteria – no easy task. The vaccine contains peptide fragments of the M protein that are genetically linked together like a string of pearls, represented in four vaccine proteins that contain a total of 30 different emm types of GAS.
“It’s the most complex vaccine that has ever been administered to humans because of the need to represent multiple different types of group A strep so that we can achieve potential coverage of the infections that cause most of the disease,” said Dale. “Thirty years ago, we knew that the M protein, which is the vaccine antigen, could protect animals against infection, but we didn’t know how to configure vaccines, because we didn’t have the technology to do it. In a sense, we had to wait for technology to catch up with our ideas.”
To date, Dale and his team have conducted four clinical trials with three different vaccines in the U.S. and Canada. The first version of the vaccine was 6-valent, while the next iteration was 26-valent. Now, StreptAnova is 30-valent and is undergoing clinical trials with positive results. In the most recent Phase 1 trial, 23 adults were vaccinated with no safety issues and the vaccine elicited the desired antibody response and was well tolerated.
Looking ahead, Dale is collaborating with investigators from UT Knoxville, Oak Ridge National Laboratories and the University of Alabama, Huntsville, to further develop the vaccine. Using structural chemistry and biology, his team is seeking to better understand peptide structures and how to analyze these structures and their functions. They have modeled versions of the vaccine that are no larger than the current 30-valent vaccine but could cover anywhere from 80 to 85 percent of all infections.
“We’re blending vaccinology with structural chemistry or structural immunology. We are learning how to configure a vaccine that would be maximally effective using a minimal number of peptide antigens,” said Dale. “Structure-based design allows us to predict which peptides are most likely to elicit cross-protective antibodies against M types of GAS that are not part of the vaccine. The next generation of StrepAnova may be even more efficacious and provide broader coverage.”
Following a recently ended commercial partnership with local company Vaxent, Dale and UTRF are seeking a new partner to carry this work forward. Dale has been thankful for the support of the university and UTRF, since his first invention disclosure in 1982.
“Dr. Jim Dale is world-renowned for his research on group A streptococcus and dedication to creating and commercializing a vaccine that would save countless lives around the globe,” said UTRF Technology Manager James Parrett. “UTRF has been pleased to work with Dr. Dale for many years. We look forward to what comes next.”