Vaginal lactobacilli in the prevention of HSV-2 infection.

Humans live in symbiosis with a tremendous number of bacteria, collectively referred to as the microbiota, that play a key role in several host physiological processes and health. While the gut microbiota has received plenty of attention the past decades, the vaginal microbiota is only recently gaining interest as a crucial player in female and reproductive health. The vaginal microbiota of most healthy women is generally dominated by Lactobacillus species, recognized as a biomarker species for vaginal health. These species also play an indispensable role in supporting the host’s defence against a wide variety of bacterial, fungal and viral pathogens. However, a detailed molecular understanding of their adaptation to the vaginal niche and their health promoting and anti-pathogen effects is currently lacking. The goal of this PhD project is therefore to deliver insights on the molecular mechanisms used by lactobacilli to contribute to vaginal health, and to defend against herpes simplex virus type 2 (HSV-2), the main causative agent of genital herpes disease, as a case study viral pathogen in the vaginal tract.

Residing at the port of entry of various pathogens causing urogenital and sexually transmitted infections in women, lactobacilli could promote vaginal health by enforcing the vaginal barrier function against these pathogens. As the vaginal barrier is composed of the vaginal epithelium, mucus and the immune system, this PhD research investigated interactions of lactobacilli with the host such as adhesion and immunomodulation as key properties to a healthy vaginal environment. Ultimately, this knowledge will drive more targeted selection criteria for probiotic strains focused on the maintenance/restoration of vaginal health.

Given that a vaginal microbiota not dominated by lactobacilli has been identified as a risk factor for HSV-2 infections, a second part of this research focused on the elucidation of putative antiviral mechanisms of action of lactobacilli against HSV-2. Hereto, a platform to study interactions between bacteria, cells and viruses was developed, representing a significant technical challenge of this project. Three antiviral mechanisms were investigated: (1) co-aggregation with virions thereby preventing host cell invasion, (2) competition with attachment/entry receptors of HSV-2 thereby blocking virus adhesion, and (3) stimulation of the innate antiviral immune response of vaginal epithelial cells following viral challenge. Next to delivering pioneer work on Lactobacillus-virus interactions at the molecular level, this PhD findings open new perspectives for microbial management-based prevention and treatment strategies against HSV-2 and potentially other vaginal infections.