Dr. Darville’s lab is actively focused on developing a vaccine to protect against Chlamydia trachomatis infection-induced sequelae of infertility and blindness, diseases of global societal and economic impact. Through in-depth analysis of T cell and antibody responses to natural genital infections in women, the lab has identified key chlamydial antigens that are both immunodominant and immunoprevalent. These antigens are now being tested in murine preclinical vaccine trials, utilizing adjuvanted recombinant proteins, viral vectors, and mRNA vaccine platforms. The team is also investigating the immune mechanisms responsible for the protective effects observed with promising vaccine candidates. 

In collaboration with Vaxcyte, Inc. and the University of Chicago, under a NIH U01-funded grant, the team has developed a novel strategy for generating subunit vaccines conjugated directly to Toll-Like Receptor (TLR) or STimulator of INterferon Genes (STING) agonists. This approach enhances mucosal immune responses by promoting antigen-presenting cell activation through coincident stimulation, resulting in reduced toxicity, improved immunogenicity, and superior efficacy. The approach also has the potential for dose-sparing and cost reduction, with the ultimate goal of advancing to human clinical trials. 

The lab is also exploring immune cell phenotypes, protein, mRNA, and miRNA responses in peripheral blood, cervical, and endometrial samples from sexually exposed women to identify biomarkers that indicate a higher risk of chlamydial infection spreading to the upper genital tract or recurring. Collaborating with Xiaojing Zheng, PhD, the team is uncovering host genetic and immune markers that may signal altered risk for C. trachomatis infection and disease. In partnership with Catherine O’Connell, PhD, and colleagues at NC State, they are also examining host-chlamydial-microbiome interactions in cervical samples from infected women to better understand factors influencing the risk of infection and ascension to the upper genital tract. 

The lab is further advancing research on collaborative cross (CC) mouse strains for vaccine testing. Pilot studies have identified strains with varying infection outcomes and pathologies, providing an excellent platform for assessing vaccine candidates and discovering conserved correlates of protection. Using a simple, cost-efficient probe-based transcriptional profiling method inspired by scRNAseq technologies, the team is examining immune responses across different CC mouse strains. This research integrates cutting-edge technologies and computational methods to refine murine models, enhancing the understanding of immune responses during primary chlamydial infection or after infectious challenge of vaccinated mice. The identification of transcriptional biomarkers has significant potential for translating findings into human vaccine studies. 

In addition to the research performed within the Darville Lab, UNC’s Pediatric Infectious Disease faculty study many other topics across the field, including HIV, Hepatitis B and antimicrobial stewardship. Read more >>