eCite Digital Repository

Immunization strategies producing a humoral IgG immune response against devil facial tumor disease in the majority of Tasmanian devils destined for wild release

Citation

Pye, R and Patchett, A and McLennan, E and Thomson, R and Carver, S and Fox, S and Pemberton, D and Kreiss, A and Baz Morelli, A and Silva, A and Pearse, MJ and Corcoran, LM and Belov, K and Hogg, CJ and Woods, GM and Lyons, AB, Immunization strategies producing a humoral IgG immune response against devil facial tumor disease in the majority of Tasmanian devils destined for wild release, Frontiers in Immunology, 9 Article 259. ISSN 1664-3224 (2018) [Refereed Article]


Preview
PDF
2Mb
  

Copyright Statement

Copyright 2018 the Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

DOI: doi:10.3389/fimmu.2018.00259

Abstract

Devil facial tumor disease (DFTD) is renowned for its successful evasion of the host immune system. Down regulation of the major histocompatabilty complex class I molecule (MHC-I) on the DFTD cells is a primary mechanism of immune escape. Immunization trials on captive Tasmanian devils have previously demonstrated that an immune response against DFTD can be induced, and that immune-mediated tumor regression can occur. However, these trials were limited by their small sample sizes. Here, we describe the results of two DFTD immunization trials on cohorts of devils prior to their wild release as part of the Tasmanian Government's Wild Devil Recovery project. 95% of the devils developed anti-DFTD antibody responses. Given the relatively large sample sizes of the trials (N = 19 and N = 33), these responses are likely to reflect those of the general devil population. DFTD cells manipulated to express MHC-I were used as the antigenic basis of the immunizations in both trials. Although the adjuvant composition and number of immunizations differed between trials, similar anti-DFTD antibody levels were obtained. The first trial comprised DFTD cells and the adjuvant combination of ISCOMATRIX™, polyIC, and CpG with up to four immunizations given at monthly intervals. This compared to the second trial whereby two immunizations comprising DFTD cells and the adjuvant combination ISCOMATRIX™, polyICLC (Hiltonol®) and imiquimod were given a month apart, providing a shorter and, therefore, more practical protocol. Both trials incorporated a booster immunization given up to 5 months after the primary course. A key finding was that devils in the second trial responded more quickly and maintained their antibody levels for longer compared to devils in the first trial. The different adjuvant combination incorporating the RNAase resistant polyICLC and imiquimod used in the second trial is likely to be responsible. The seroconversion in the majority of devils in these anti-DFTD immunization trials was remarkable, especially as DFTD is hallmarked by its immune evasion mechanisms. Microsatellite analyzes of MHC revealed that some MHC-I microsatellites correlated to stronger immune responses. These trials signify the first step in the long-term objective of releasing devils with immunity to DFTD into the wild.

Item Details

Item Type:Refereed Article
Keywords:Tasmanian devil facial tumour disease, adjuvant, humoral immunity/antibody response, vaccination, wild immunology
Research Division:Medical and Health Sciences
Research Group:Immunology
Research Field:Humoural Immunology and Immunochemistry
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Immune System and Allergy
Author:Pye, R (Dr Ruth Pye)
Author:Patchett, A (Miss Amanda Patchett)
Author:Carver, S (Dr Scott Carver)
Author:Kreiss, A (Dr Alexandre Kreiss)
Author:Woods, GM (Professor Gregory Woods)
Author:Lyons, AB (Dr Bruce Lyons)
ID Code:125238
Year Published:2018
Funding Support:Australian Research Council (LP130100218)
Deposited By:Menzies Institute for Medical Research
Deposited On:2018-04-09
Last Modified:2018-05-02
Downloads:3 View Download Statistics

Repository Staff Only: item control page