Vaccination with recombinant oncosphere antigens reduces the susceptibility of sheep to infection with Taenia multiceps

Abstract

Taenia multiceps is a cestode parasite, the larval stage of which encysts in the brain of sheep, goats and cattle causing an often fatal condition. The parasite also causes zoonotic infections in humans. Homologues of the recombinant oncosphere vaccine antigens from Taenia ovis and other Taenia species were identified in T. multiceps. Sequencing of the associated T. multiceps genes and cloning of the encoding mRNA has revealed conserved features in the genes and proteins. The T. multiceps oncosphere proteins, designated Tm16 and Tm18, contain a predicted secretory signal and fibronectin type III domain. The recombinant Tm16 and Tm18 proteins were successfully expressed in Escherichia coli as fusion proteins with GST. The antigens, formulated with Quil A adjuvant, were tested in a vaccine trial in sheep. The antigens stimulated immunity in sheep against challenge infection with T. multiceps eggs. Five of nine control sheep died due to a challenge infection with T. multiceps whereas none of 20 vaccinated animals died as a result of the parasite challenge (P = 0.001). In addition, vaccination with the Tm16 protein, or Tm16 plus Tm18, induced significant protection against the number of parasites encysting in the brain as a result of the challenge infection (P = 0.023, P = 0.015, respectively). No clear relationship was apparent between the level of specific serum antibody in vaccinated animals and either the presence or absence of parasites or the number of parasites that occurred in some of the vaccinated animals. We believe this study is the first description of recombinant vaccine-related investigations for T. multiceps. The recombinant oncosphere antigens identified may allow development of effective vaccination strategies against T. multiceps infection in sheep. They raise the potential for the development of a combined vaccine with the Echinococcus granulosus EG95 antigen for prevention of T. multiceps as well as preventing the transmission of cystic hydatid disease.

Clinical, pathological and molecular evaluations and CT scan screening of coenurosis (Coenurus cerebralis) in sheep and calves

“…The transmission of a hydatid infection to humans could be reduced by the extensive use of this vaccine. Recently, Gauci et al (2008) described the development of a vaccine against T. multiceps. The vaccine utilizes oncosphere antigens that are homologues of known host-protective proteins of other Taenia species (LIGHTOWLERS, 2006).…”

Clinical evolution of cerebral coenurosis from invasive to chronic infection in sheep and a goat

“…The adult worm inhabits the small intestine of canids while the larval stage develops in the central nervous system (CNS) of ruminants [3,4]. The disease occurs in acute, quiescent, and chronic forms [5][6][7]. Though coenurosis can be controlled by anthelmintic treatment of dogs and by correctly disposing carcasses [8], surgical removal of cysts is the only effective therapy to date.…”

“…Post-mortem examinations in acute coenurosis have demonstrated necrotic lesions in the brain characterized by immature metacestode, 2 to 4 mm diameter, surrounded by hemorrhagic foci up to 2 mm wide [17]. The principal immune response against taeniid cestodes in their intermediate hosts is antibody and complement mediated lysis of the early developing oncosphere [19][20][21]; these features have been used to develop recombinant antigens for vaccination against T. multiceps in sheep [5,6]. However, complete cystic resorption is described here for the first time.…”

Vaccine development against theTaenia soliumparasite

“…14,21,22 This strategy was adopted after it was discovered, serendipitously, that a similar approach improved the stability of a related parasite antigen expressed in E. coli. The 45W protein from Taenia ovis 23 was among the first vaccine antigens found to be expressed at higher levels in E. coli following deletion of cDNA sequence encoding a carboxy terminal region comprising mainly hydrophobic amino acids.…”

“…These modifications were prepared prior to the development of PCR methods; with the advent of PCR it has been possible to truncate recombinant antigens by precise removal of codon regions corresponding to specific amino acids. 14,21,22 Recent advances in gene synthesis technology 26 now makes it possible to reduce the effort required to prepare modified genetic constructs and, where gene sequence is available, there would be no requirement for isolation of mRNA encoding the antigen of interest.…”