Structure, Immunity, Microbiome: 3D Biomimetic Cervicovaginal Models of Sexually Transmitted Infections (SIM-STI)

The well-travelled aphorism “Essentially, all models are wrong, but some are useful” enunciated by statistician George E.P. Box in 1979 is rarely more appropriate than when applied to the study of infectious diseases. Two interrelated questions emerge from Box’s words: How close can a model come to the original? And How to make a model as useful as possible? The answers to these two closely linked fundamental questions are the essence and the challenge of the NIH-NIAID funded Biomimetics Cooperative Research Center (CRC) Structure, Immunity, Microbiome: 3D Biomimetic Cervicovaginal Models of Sexually Transmitted Infections (SIM-STI), co-directed by Drs. Jacques Ravel (UMB Institute for Genome Science), Jason Gleghorn (University of Delaware), and Patrik Bavoil (UMB).

The overarching objective of SIM-STI is to bridge the gap currently existing between our understanding of chlamydial and gonococcal infections derived from animal and cellular models, and from ex vivo data, and that generated from observing the actual infection and disease occurring in humans. For this, SIM-STI leverages significant recent advances in tissue engineering under the leadership of Dr. Jason Gleghorn, U Delaware, as well as advances in microbiome research led by Dr. Jacques Ravel, UMB Institute for Genome Sciences. The overall significance of SIM-STI is the elimination of the leap of faith – or reduction to a small hop – currently necessary to bridge this gap. The extended significance is that SIM-STI represents the first of a new generation of model systems to study infection and disease in the human reproductive tract, to serve as a translational platform to evaluate interventions against STIs for the benefit of public health, and finally, for itself to serve as a model in the study of other mucosal diseases, infectious, chronic or otherwise. SIM-STI includes a research project led by Drs. Jacques Ravel and Vonetta Edwards, U Maryland, and Larry Forney, U Idaho, as well as two projects respectively led by Drs Isabelle Derré and Alison Criss, U Virginia.

The ultimate impact of this research will be to improve public health by reducing the incidence of STIs in humans. In the United States, C. trachomatis genital infections are the most frequently reported bacterial infectious disease with 1.8M cases reported in 2019 (~3M estimated) and rising yearly by several percent. Likewise, there were 616K reported cases of N. gonorrhoeae (including rapidly emerging antibiotic resistant strains. The sequelae of infections and co-infections caused by C. trachomatis and N. gonorrhoeae account for the majority of the estimated over 1M yearly cases of pelvic inflammatory disease in the United States, a precursor to infertility in women and life-threatening ectopic pregnancy. Thus, SIM-STI research will ultimately provide broad health and economic benefits.