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Capturing complex vaccine-immune-disease relationships for free-ranging koalas: higher chlamydial loads are associated with less IL17 expression and more chlamydial disease

Citation

Lizarraga, D and Timms, P and Quigley, BL and Hanger, J and Carver, S, Capturing complex vaccine-immune-disease relationships for free-ranging koalas: higher chlamydial loads are associated with less IL17 expression and more chlamydial disease, Frontiers in Veterinary Science, 7 pp. 1-12. ISSN 2297-1769 (2020) [Refereed Article]


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Copyright Statement

Copyright 2020 Lizárraga, Timms, Quigley, Hanger and Carver Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

DOI: doi:10.3389/fvets.2020.530686

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.

Item Details

Item Type:Refereed Article
Keywords:structural equation model; Chlamydia; vaccine; koala; cytokine
Research Division:Agricultural, Veterinary and Food Sciences
Research Group:Veterinary sciences
Research Field:Veterinary parasitology
Objective Division:Environmental Management
Objective Group:Terrestrial systems and management
Objective Field:Control of pests, diseases and exotic species in terrestrial environments
UTAS Author:Lizarraga, D (Mr David Lizarraga)
UTAS Author:Carver, S (Dr Scott Carver)
ID Code:149654
Year Published:2020
Funding Support:Australian Research Council (LP160100138)
Web of Science® Times Cited:1
Deposited By:Zoology
Deposited On:2022-04-05
Last Modified:2022-05-05
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