Development of Experimental Vaccines Against Liver Flukes
A multitude of experimental vaccines have been developed against liver flukes in the past. However, there has yet to be the development of a commercial livestock vaccine. Reasons for this may be multiple, and include the lack of identification of the best
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Introduction Fasciolosis is a disease caused by the Fasciola genus where Fasciola hepatica and Fasciola gigantica are predominantly found in temperate and tropical climates, respectively. Fasciolosis is traditionally regarded as a disease that affects ruminants which causes large economic losses in the agriculture sector, previously estimated at US$ three billion annually [1], but likely to be far higher currently. In the last 20 years, it has also emerged as an important human zoonosis with an estimated 2.4 million people infected worldwide [2, 3]. In addition, cases of resistance to the drug of choice against fasciolosis, triclabendazole, have been reported in farms of many countries in Europe and in Australia [4–6]. The emergence of triclabendazole-resistant flukes has urged the discoveries of new alternatives to control fasciolosis. Liver flukes sophisticatedly manipulate the host immune system to maintain their long term survival in the host by shifting the host immune response towards Th2-type, which is anti-inflammatory and promotes wound healing [7–9]. Th1 and Th2-type associated responses in the murine system are reflected by IgG2a and IgG1 isotypes, respectively [10]. The possible requirement of a Th1-type immune response to resist liver fluke infections has been demonstrated in sheep and cattle as IgG2 antibody levels were associated with lower liver flukes recoveries [11, 12]. However, all is not as simple as it seems, as in another study, low levels of IgG2 in sheep were seen as protective [13]. Previously, the efficacy of multivalent vaccines created by combining different cathepsin proteases, DNA vaccines constructed with cathepsin protease encoding genes, and single protein vaccines
Sunil Thomas (ed.), Vaccine Design: Methods and Protocols, Volume 2: Vaccines for Veterinary Diseases, Methods in Molecular Biology, vol. 1404, DOI 10.1007/978-1-4939-3389-1_9, © Springer Science+Business Media New York 2016
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Huan Yong Yap and Peter M. Smooker
with various excretory/secretory products as targeted antigens have been evaluated in different studies [14–18]. A protein vaccine with leucine amino peptidase (LAP) as a targeted antigen in alum adjuvant is the only vaccine that fulfilled the requirement to be a commercial vaccine as it appears to have efficacy that has reached the required level and the antigen is delivered in a commercially acceptable adjuvant [14, 19, 20]. Interestingly, the proposed protective pro-inflammatory immune responses induced by this vaccine are low, as indicated by a high IgG1/IgG2 ratio [20]. This would indicate that depending on the antigen, Th2 responses may also be protective. Parasites secrete various proteases at different stages of their life cycle to facilitate parasitism and maintain their long term survival in the host. In F. hepatica , cathepsin B protease is expressed in the infectious metacercariae and in newly excysted juveniles while cathepsin L isoforms are secreted throughout the life cycle of liver flukes, and more than 80 % of proteins secreted by a
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