In cattle, endogenous transplacental infection from a pregnant dam to its unborn foetus is considered to be the predominant route of transmission [2-4]. Cows of any age may abort from three-month gestation to term with most abortions occurring at five to six month of gestation [5]. A number of compounds have been evaluated for the potential treatment of neosporosis, but none of these have demonstrated efficacy in cattle [6-12], leaving the development of a vaccine as an attractive alternative. A commercialized vaccine (Neoguard™) composed

of tachyzoite lysate was introduced in the United States, but has been taken off the market again due to ambiguous efficacy data [13, 14]. One of the strategies for developing a vaccine against neosporosis Enzalutamide research buy has been to focus on antigens that are involved in tachyzoite adhesion and invasion of host cells. These are antigens localized on the surface of tachyzoites or within secretory organelles such as micronemes, rhoptries and dense granules [15]. Protein disulphide isomerase in N. caninum tachyzoites

(NcPDI) is found within micronemes and on the tachyzoite surface [16]. Antibodies directed against recombinant NcPDI, as well as commercially available PDI inhibitors, impaired host cell invasion by N. caninum [16]. Besides the choice of antigen, the route of application and adjuvant are of prime importance. We have previously shown that intranasal vaccination buy MG-132 of mice with recNcPDI emulsified in cholera toxin (CT) BGB324 order adjuvant resulted

in high (90%) protection against clinical signs of disease and significantly decreased cerebral parasite load in nonpregnant mice, while intraperitoneal vaccination was ineffective [17, 18]. Cholera toxin is comprised of two subunits, A and B, arranged in an AB5 configuration. The toxic A subunit is an ADP-ribosyltransferase, which disrupts the proper signalling of G proteins and eventually leads to dehydration of the cell. The nontoxic B subunit mediates the binding of CT to cellular surfaces via the pentasaccharide chain of ganglioside GM1 [19]. CT is a powerful mucosal adjuvant, which potentiates the immunogenicity of most antigens, no matter whether they are crosslinked or simply mixed with CT. Among many effects, CT leads to enhanced presentation by various antigen-presenting cells (APC) such as dendritic cells, macrophages and B cells. It has been claimed that CT primarily induces Th2-type immune responses characterized by CD4+ T cells producing IL-4, IL-5, IL-6 and IL-10 and by the production of IgA, IgG1 and IgE antibodies [20, 21]. However, other studies have shown that CT can also induce mixed Th1 and Th2 type of immune responses. As CT is normally considered to be toxic, great efforts have been made to separate the adjuvant and toxic activities as a basis for the development of mucosal adjuvants [22].