Assessing Tissue-Specific Female Upper Genital Tract Pathology During Chlamydia Infection: Inter-rater Reliability and Virus-Like Particle Vaccine Strategies

Abstract

Chlamydia is the world’s most prevalent bacterial sexually transmitted pathogen. Chlamydia disproportionately affects people with uteri, inducing severe chronic pathology in the female genital tract if untreated. Because prophylactic screening is limited, it is imperative to develop a safe, accessible, effective Chlamydia vaccine. Prior work links the Chlamydia putative cytotoxin CT166 to chronic oviduct pathology in mice. This research tests CT166 as an antigen in a Virus-Like Particle (VLP) vaccine, QB-CT166, against Chlamydia muridarum infection. Here we show that QB-CT166 induces high titers of IgG in the serum but low levels of IgG in the vagina and uterus. We reveal that the vaccine does not reduce Chlamydia bacterial burden nor immunopathology. In parallel with this vaccinology research, we sought to fill a gap in the literature by developing a reliable, teachable Chlamydia pathology scoring system. We analyzed the reliability of pilot scales and optimized them to be clear and biologically representative, then tested their teachability with a training intervention for new lab members. This project yielded resources for members during training and pathology scoring and identified an inter-rater reliability analysis method to ensure future scoring robustness. This work moves the Chlamydia field forward through insights into vaccinology and inter-rater reliability.