Capturing complex vaccine-immune-disease relationships for free-ranging koalas: IL17 production is an important intermediate factor against chlamydial disease

Abstract

Background Disease is a major factor negatively affecting koala populations. Vaccination is a promising treatment option that would result in immune-mediated protection against disease. Measuring and assessing vaccine efficacy can be challenging owing to both direct and indirect interactions caused by vaccination. In this study, we investigate vaccine-immune-chlamydial load-disease relationships from MOMP (major outer membrane protein) vaccine trials to protect healthy free-ranging koalas against Chlamydia -related diseases. Methods We created a priori hypotheses based on data sources and perceived direct and indirect interactions from koalas vaccinated six months prior. Each hypothesis was tested as a structural equation model to evaluate possible causality among measured variables. Model averaging was used as multiple models fit the data, and the strength of relationships were examined through averaged coefficients and the raw data. Results Despite multiple potential sources of variation owing to the koalas in this study being free-ranging, our analyses provide unique insights into the effects of vaccinating against Chlamydia . We found more relationships in urogenital models with interleukin 17 (IL17) production compared to models with interferon gamma (IFNγ) production. In the averaged model with IL17, urogenital chlamydial load was positively associated with disease and negatively associated with IL17 production. MOMP vaccination had a trending effect for reducing chlamydial load and also had a strong effect on increasing IL17 production. This indicated a link between MOMP vaccination, reduction of urogenital chlamydial load, and increased production of IL17. Not surprisingly, urogenital chlamydial load was a positive predictor for the development of urogenital disease at six months post-vaccination. Conclusions Using structural equation modelling, this study has helped illuminate that the immune cytokine IL17 may be an important intermediate factor linking MOMP vaccination with chlamydial pathogenesis and protection, enhancing previous investigations. Going beyond univariate statistics, the methods used in this study can be applied to other preclinical vaccination experiments to identify important direct and indirect factors underpinning the effects of a vaccine.

Capturing Complex Vaccine-Immune-Disease Relationships for Free-Ranging Koalas: Higher Chlamydial Loads Are Associated With Less IL17 Expression and More Chlamydial Disease

“…We thank the many groups that supported the overall koala data collection, specifically, for collecting the data published in Waugh et al (19) and Desclozeaux et al (20), respectively, that were used in the current study. This manuscript was previously posted as a pre-print on ResearchSquare, Lizárraga et al (54), and updated upon the authors request for its withdrawal, Lizárraga et al (55).…”