Abstract
Background: Chlamydial disease is a major factor negatively affecting koala populations. Vaccination is a promising management 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 6 months prior. Each hypothesis was tested as a structural equation model separately for either the urogenital or the ocular site to evaluate possible causality among measured variables. Model averaging was used as multiple models fit the data, and the strength of relationships was examined through averaged coefficients and the raw data.Results: We found more relationships in urogenital models as compared to ocular models, particularly those with interleukin 17 (IL17) mRNA expression compared to models with interferon gamma (IFNγ) expression. In the averaged model with IL17, urogenital chlamydial load was positively associated with disease and negatively associated with IL17 expression. MOMP vaccination had a trending effect for reducing urogenital chlamydial load and also had a strong effect on increasing IL17 expression. Not surprisingly, urogenital chlamydial load was a positive predictor for the development of urogenital disease at 6 months post-vaccination.Conclusions: 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. Using structural equation modeling, this study has helped illuminate that the expression of the immune cytokine IL17 is linked to MOMP vaccination, and animals with a high urogenital chlamydial load expressed less IL17 and were more likely to develop disease, 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.
Highlights
Koala (Phascolarctos cinereus) populations, in the Australian Capital Territory and in the Australian states of New South Wales and Queensland, have suffered staggering losses over recent years [1,2,3,4] leading to their conservation status being listed as “vulnerable” per the IUCN [5]
As we found no evidence supporting a difference between the two trials, we pooled the data to obtain sample sizes sufficient to use in structural equation models
We found that major outer membrane proteins (MOMP) vaccination may indirectly affect the development of urogenital disease in koalas by inhibiting the growth of Chlamydia
Summary
Koala (Phascolarctos cinereus) populations, in the Australian Capital Territory and in the Australian states of New South Wales and Queensland, have suffered staggering losses over recent years [1,2,3,4] leading to their conservation status being listed as “vulnerable” per the IUCN [5]. A number of factors negatively affect koala populations including: habitat loss [1, 6], climate change [7], bushfires [8], motor vehicle accidents [6], dog attacks [8], and disease [9]. The magnitude of disease-related mortality within a given population is potentially exacerbated by environmental stressors including climate change, habitat loss resulting from urbanization, and environmental disasters such as bushfires, though to our knowledge no study has investigated this in wild koala populations [10]. Modeling by Craig et al [17] suggested that chlamydial vaccination could stabilize koala populations after 5 years of using a vaccine (with protective efficacy of 75%) administered to around 10% of koalas per year. 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
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