Recent history of Veterinary Immunology in Australia

This Commentary article reviews the history of veterinary immunology in Australia from the 1980s and discusses the key people and areas of research during this period.

Veterinary immunology in Australia was greatly advanced with the development of monoclonal antibody (mAb) technology in the late 1970s.Mal Brandon was instructed in the production of mAbs by fellow Australian Alan Williams, at the Sir William Dunn School of Pathology in Oxford, and brought the technology back to Melbourne University's School of Veterinary Science in 1981.With a cohort of PhD students, most notably Charles Mackay and Jill Maddox, he produced a large range of mAbs against sheep and cattle lymphocyte surface antigens which were distributed to laboratories worldwide. 1These reagents facilitated basic studies of immune development in sheep, 2 and, in collaborations with Ross Cahill and Wayne Kimpton, the recirculation of lymphocyte subsets using lymph node cannulation technologies pioneered by Bede Morris and Alex Lascelles in the 1960s. 3One highlight of these studies was the discovery of a third lymphocyte subset, highly prevalent in the peripheral blood of ruminants and not reported in any other species. 4his cell population, defined by mAb 19-19, was later identified as a cd T cell.Recirculation studies also showed for the first time the differential migration of lymphocyte subsets. 5,6ith the recruitment of Els Meeusen, immunological studies were expanded to parasite immunology and, in collaboration with anatomist CS Lee, reproductive immunology.As well as increasing our understanding of immunity against the major sheep parasites, these studies led to the discovery of a novel technique for identifying stage-specific antigens using antibodies secreted by in vivo-induced antibody-secreting cells. 7This "ASC-probe" technology was used to identify vaccine candidates against bacterial (John Walker) 8 and helminth (Vern Bowles, Hamish McWilliam) 9,10 infections and, more recently, tumor-associated antigens. 11Immunological studies of the ovine placenta revealed the dramatic increase of a highly granular cd T-cell population at late stages of pregnancy with antimicrobial and cytotoxic properties, indicating their role in the protection of the womb during parturition. 12ith the application of the latest molecular technologies, Jill Dunphy discovered two new immune mediators involved in immunological responses to parasite infections, galectin-10 13 and galectin-11. 14][17] In recognition of its increasing international reputation, Dr Brandon's group was designated an independent "Centre for Animal Biotechnology" (CAB) within the School of Veterinary Sciences at Parkville in 1990.At the same time, a new group was established within CAB to apply the new field of cytokines to veterinary research, headed by Andrew Nash.This group was highly productive in generating recombinant cytokines and anti-cytokine/receptor antibodies and examining their role as potential immunological adjuvants. 18,19Further vaccine and adjuvant studies, led by Jean-Pierre Scheelinck, were conducted using sheep as a large animal model, including the novel DNA vaccination technique. 20al Brandon remained Director of the CAB until 1999 when he left to take up commercial opportunities.He was replaced as Director by Els Meeusen until 2006 when she moved with her group to set up the Biotechnology Research Laboratories (BRL) at Monash University.At BRL, the parasite vaccine research was headed by David Piedrafita and resulted in the first successful field study of a defined larval vaccine against Haemonchus contortus. 21,22More fundamental research to understand the action of vaccine adjuvants was conducted by Mike de Veer, using the unique sheep cannulation models 23-25 (Figure 1).
During this time, a significant breakthrough in parasite vaccines was produced by Mike Rickard's group at the Werribee site of Melbourne University's School of Veterinary Sciences.In collaboration with David Heath in New Zealand, they achieved the first successful experimental vaccine against a helminth parasite (Taenia ovis) using a single recombinant antigen, which was published in a 1989 Nature paper. 26This vaccine approach was followed up and expanded to several other important cestode infections by Marshall Lightowlers, with successful trials in many developing countries (reviewed by Lightowlers 27 ).This led to the development and registration of a vaccine in pigs for Taenia solium (Cysvax), which has been used to reduce transmission of this parasite to humans. 28xtensive These included vaccination with a range of larval and adult antigens, and depletion of immune cells and cytokines during infections. 29 unique approach to parasite vaccines was to ignore the (often poor) natural immunity and generate an immune response against so-called hidden antigens (i.e.molecules that do not naturally induce a protective immune response but that, when targeted, interfere with essential processes of the parasite).The first successful application of this technology was applied by Peter Willadson's group at CSIRO in Queensland against the cattle tick, using vaccination with tick gut extract.The antigen responsible for protection was identified as the Bm86 protein, produced by recombinant technology 30 and commercialized as "Tick-GARD" in 1994.A similar approach against another bloodsucking parasite, H. contortus, was pursued by Sue Newton and her group at the Department of Agriculture in Victoria. 31While very high levels of protection were achieved with the native gut formulation (H11), attempts at vaccinations with different recombinant proteins were not successful.
Prospects for developing vaccines against the major parasitic trematode of cattle, Fasciola hepatica, are generally considered very poor, as no natural immunity has been documented against this parasite.However, extensive studies by Terry Spithill, Herman Raadsma, Jill Pleasance and David Piedrafita, with the Indonesian variant F. gigantica, showed that some natural immunity does exist. 32Through comparative studies, they elucidated some of the immunological differences that may form the key to potential future control strategies. 33,34n unusual, but very Australian, immunization protocol was trialed by Greg Woods' group at the University of Tasmania against devil facial tumor disease.Using a combination of in vitro-stimulated tumor cells and cytokine therapy, they were able to show some immune-mediated regression of established tumors. 35he CSIRO Animal Health group at Parkville worked closely with several industry groups to develop vaccines and diagnostics for poultry and ruminants.Kevin Fahey led the avian infectious disease group along with Mike Sheppard, Steven Prowse, Wojtek Michalski, Jagoda Ignjatovic, John Lowenthal, Pete McWaters, Jenny York, Jackie Pallister and Trevor Bagust.The group's major project, led by Fahey, identified the protective subunit of infectious bursal disease virus which, in collaboration with Ahmed Azad and Ian Macreadie in the CSIRO Division of Biochemistry, was expressed in the yeast Saccharomyces cerevisiae to produce a recombinant subunit vaccine for breeding hens that passively protected their progeny via antibody in the egg yolk. 36Arthur Webster financially supported much of this research, which became a major development project for Webster's prior to the company being acquired by the US company Merial.Studies on infectious laryngotracheitis virus (ILTV), led by Jenny York, showed that mucosal antibody to this herpesvirus was protective and that it was the glycoproteins of the virus that stimulated this protection. 37esearch was also undertaken by Chris Prideaux, Kritaya Kongsuwan and Mike Johnson to develop ILTV as a vaccine vector for protective immunogens of other viruses. 38riginal research by Jackie Pallister and Mike Sheppard was the first to show that the fiber protein of fowl adenovirus was responsible for the variations in the virulence of these viruses.Prowse and Michalski worked toward making recombinant subunit vaccines to the parasite Eimeria tenella in collaboration with Biotechnology Australia (Pty Ltd), 39 while Katrina Erny identified highly virulent adenovirus that induced inclusion body hepatitis in chickens. 40Pallister and Sheppard also cloned and expressed the thenunclassified chicken anemia virus to develop an ELISA screening assay to detect infected chickens. 41mmunological reagents were also generated in chickens to conduct immunological studies at the CSIRO Biosecurity Laboratories in Geelong, Victoria, by John Lowenthal, Andrew Bean et al. 42,43 These studies have become particularly relevant in recent years, with several zoonotic viral infections originating in birds (avian influenza). 44,45ony In 1993, the Cooperative Research Centre for Vaccine Technology was created with Michael Good (QIMR) as the Director and Paul Wood as the Deputy Director.The Cytokine Biology group became part of the CRC-VT and expanded its focus to also work on DNA vaccines (Rob DeRose, Nick Kennedy, Jan Tennent), 50 foot rot (Jackie Hunt), 51 Anaplasma (Kevin Gale), 52 adjuvants (Mike Rifkin) and porcine cytokines (David Strom).

O Ovine Lymphatic Cannulation Model
An interesting vaccination strategy pursued by John Walker's group at CSL/Pfizer AH was to target specific hormones involved in sexual development for reproduction control.T-cell help to these hormone peptides was provided by conjugation to whole proteins or defined T-cell helper epitopes.Using this approach and with a suitable adjuvant, an effective commercial LHRH (gonadotropinreleasing hormone) vaccine was produced for pigs and horses (Improvac/Equity). 53,54ost of the early work promoting veterinary immunology was supported by grants from the rural industries (e.g.Meat & Livestock, Wool Corporation) and commercial companies (CSL, Websters, Pfizer AH), with an emphasis on tackling issues of animal health and production.More recently, veterinary species (in particular, sheep in Australia) have become more recognized as valid models for studying human diseases (between mice and man).In addition, large animals provide some unique technologies (e.g.lymph node cannulation) and opportunities for studying physiological and immunological processes from a whole-animal perspective.This has been reflected in the "One-Health" approach taken up by many organizations (e.g.Centers for Disease Control and Prevention, World Health Organization), which should promote more collaboration between veterinary, human and smallanimal immunologists.

Figure 1 .
Figure 1.Ovine lymphatic cannulation models.Both efferent and (pseudo)afferent lymphatic vessels can be cannulated, allowing continuous and detailed monitoring of cells and mediators after injection or infection.Diagram credit: Els Meeusen.
Parasite Immunol 1997; 19: 411-417.53.Dunshea FR, Colantoni C, Howard K, et al.Vaccination of boars with a GnRH vaccine (Improvac) eliminates boar taint and increases growth performance.J Anim Sci 2001; 79: 2524-2535.54.Elhay M, Newbold A, Britton A, Turley P, Dowsett K, Walker J. Suppression of behavioural and physiological oestrus in the mare by vaccination against GnRH.Aust Vet J 2007; 85: 39-45.ª 2023 The Authors.Immunology & Cell Biology published by John Wiley & Sons Australia, Ltd on behalf of the Australian and New Zealand Society for Immunology, Inc.This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.