This five-year grant from the National Institute of Allergy and Infectious Diseases is led by Toni Darville, MD, director of the UNC Children’s Research Institute, in collaboration with scientists at Vaxcyte, Inc. and the University of Chicago.
CHAPEL HILL, NC – To address the global epidemic of sexually transmitted diseases, the National Institute of Allergy and Infectious Diseases has awarded a five-year, $9.3 million grant to the University of North Carolina at Chapel Hill, Vaxcyte, and the University of Chicago to develop a vaccine candidate for the prevention of Chlamydia.
Through this signficant U01 grant, a group of scientists led by Toni Darville, MD, Distinguished Professor of Pediatrics and Microbiology & Immunology, division chief of pediatric infectious diseases, and scientific director of the Children’s Research Institute at the UNC School of Medicine, will build upon their past vaccinology accomplishments to develop a viable vaccine candidate for early human clinical trials.
Darville is the principal investigator, and Jeff Fairman, PhD, vice president of research and co-founder of Vaxcyte, is a co-principal investigator. Aaron Esser-Kahn, PhD, professor of molecular engineering at the University of Chicago Pritzker School of Molecular Engineering, is a co-collaborator. Taylor Poston, PhD, at UNC, and James Rozzelle at Vaxcyte, are also key scientists dedicated to the project.
Chlamydia is a common, treatable sexually transmitted disease, but it affects many millions of people around the world, including one in 20 Americans, according to the U.S. Centers for Disease Control and Prevention (CDC). Many people never experience symptoms and never get tested for the bacterium, so may not know they have the disease. Yet, if left untreated, Chlamydia can seriously harm the reproductive system of females, making it impossible or difficult to get pregnant. If an infected female does get pregnant, the disease can lead to a potentially fatal ectopic pregnancy, which is when a pregnancy occurs outside the uterus, or severe complications during childbirth. The bacterium can also be transmitted to babies and cause eye infection and pneumonia.
“There is a clear unmet need for a vaccine to protect against Chlamydia trachomatis,” said Darville. “Our previous studies of infected women and mice identified Chlamydial Protease Activation Factor (CPAF) as a strong vaccine candidate.
Due to the nature of the female genital tract and its lack of secondary lymphoid tissue, a vaccine requires potent adjuvants to modulate the body’s immune response and help it induce effective immunity against the bacterium. Also, Chlamydia may require mucosal vaccination to ensure resident memory T cells are generated to fight the bacterium before infection sets in.
The scientists’ previous lab experiments showed that combining their vaccine candidate with specific adjuvants to alter the immune response in specific ways and other nanomolecules induced high levels of CPAF-specific CD4 T cells and protection from infection and pathology.
“Our earlier work showed that our new covalent CPAF-adjuvant conjugation approach enhanced cell activation, reduced toxicity, and improved immune response, leading to superior efficacy as well as reduced cost,” Darville said.
Fairman added, “We’re excited to explore our ability to successfully develop a Chlamydia vaccine candidate that can be advanced to early-phase human clinical trials. This grant will allow us to incorporate a tiered approach to determine if refinements using an innovative generation of molecules delivered via mucosal routes will enhance disease protection in animal models.”
This research is supported by the National Institute Of Allergy And Infectious Diseases of the National Institutes of Health under Award Number U01AI182180.
Media contact: Mark Derewicz, UNC School of Medicine, 919-923-0959.