The National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, today announced awards to establish four Cooperative Research Centers (CRCs) focused on developing vaccines to prevent sexually transmitted infections (STIs). The grants, totaling $41.6 million over five years, will support collaborative, multidisciplinary research on the bacteria that cause syphilis, gonorrhea and chlamydia. At the end of the program, each center is expected to identify at least one candidate vaccine ready for testing in clinical trials.
"STI research has recently evolved rapidly on multiple fronts, and this new knowledge can now be applied to a critical remaining challenge--the development of safe and effective vaccines for diseases that pose significant and growing public health burdens," said NIAID Director Anthony S. Fauci, M.D. "At this time, no vaccines are available to prevent syphilis, gonorrhea or chlamydia. However, research at these new centers should help fill the pipeline with several vaccine candidates that have feasible pathways to licensure in the U.S."
The centers funded through this new program all involve multiple U.S. research institutions as well as international collaborators. Each center will conduct at least three research projects organized on a common theme. The centers will be supported by scientific cores that will supply shared research services including monoclonal antibody production, microbiology laboratory services and statistical expertise.
One center, based at the UConn Health School of Medicine, will receive up to $11 million over five years to study syphilis. This center will be headed by UConn Health School of Medicine Professor Justin Radolf, M.D., and Duke University Associate Professor Michael Anthony Moody, M.D. Syphilis is the second leading cause of miscarriage and stillbirth worldwide. Left untreated, syphilis infection can lead to stroke, dementia or other neurological impairments. In 2017, 30,644 cases of early syphilis were reported in the United States, an increase of 76 percent since 2013, according to the Centers for Disease Control and Prevention (CDC). Congenital syphilis, or infections passed from mother-to-baby during pregnancy or delivery, have also surged in recent years. The study team will build on earlier findings using structural biology approaches to investigate surface-exposed proteins within the outer membrane of Treponema pallidum, the bacterium that causes syphilis, which they believe could serve as targets for a vaccine.
Two of the centers are focused on gonorrhea, an STI caused by Neisseria gonorrhoeae. More than half a million gonorrhea diagnoses were reported in the United States in 2017, an increase of 67 percent from 2013, according to the CDC. Especially concerning is the fact that the bacteria that cause gonorrhea have become resistant to most antibiotics. In recent years, the CDC reported that ceftriaxone is the only remaining highly effective antibiotic left to treat gonorrhea in the United States. In women, undiagnosed or untreated gonorrhea can lead to endometritis, pelvic inflammatory disease and infertility. Babies born to infected mothers are at increased risk of blindness.
Ann Jerse, Ph.D., of the Uniformed Services University of Health Sciences, is the principal investigator for the Gonorrhea Vaccine Cooperative Research Center (GV CRC), which will receive up to $10.7 million over five years. Four research projects in the GV CRC will study immune signals that may provide evidence that candidate gonorrhea vaccine has induced immunity. Among other projects, the team will assess samples from people and mice previously vaccinated with a candidate vaccine, 4CMenB, for which there is evidence of protection against gonorrhea.
A center based at Georgia State University and headed by Cynthia Cornelissen, Ph.D., will receive up to $9.25 million over five years. Projects at this center will focus on interfering with bacterial nutrient transport as a protective strategy against gonococcal bacteria. They plan to develop vaccine candidates that target bacterial systems needed to acquire iron and zinc, thus starving the bacteria of required nutrients. One project will model the effectiveness of possible gonococcal vaccine formulations using protein antigen diversity information, antibiotic resistance prevalence and community acceptance data.
A fourth center, based at the University of North Carolina (UNC) at Chapel Hill and led by Toni Darville, M.D., of the UNC School of Medicine, will receive up to $10.7 million over five years to advance chlamydia vaccine research. Chlamydia trachomatis is the most common sexually transmitted bacterial pathogen in the world. CDC estimates that at least 1.7 million cases of chlamydia were diagnosed in the United States in 2017, 45 percent of which were in women aged 15 to 24 years. Most infections are asymptomatic, but untreated chlamydia infections in women can lead to pelvic inflammatory disease or infertility and have been linked to ovarian cancer.
Projects planned by the UNC-Chlamydia Vaccine Initiative Cooperative Research Center include one that will follow a group of women at high risk of chlamydia re-infection for a year after antibiotic treatment to better understand immune responses to the infection. A subsequent project will use information gathered from studying women's immune system responses to chlamydia infection as a guide for developing candidate vaccines with the capacity to elicit robust T cell responses, which are believed to be essential in protecting against infection with chlamydia.