caninum (9). Despite the fact that protective measures to prevent infection have been sought, there is no nonlive vaccine capable of inducing complete protective immunity against neosporosis in cattle. Forskolin In contrast,
live vaccines such as attenuated strains of N. caninum have been shown to elicit protective immunity in cattle and mice (10,11). Despite this efficacy, live vaccines are generally not considered to be an economically viable option, because of logistic problems in production and handling, short-shelf life and the risk of reverting to a more virulent phenotype. The commercialized nonviable vaccine (Neoguard™) based on tachyzoite extracts, which is currently marketed in the Unites States of America, exhibits ambiguous results (12,13), and was shown to provide only partial protectivity (14). This could be because of the fact that a crude lysate contains immunoprotective, but possibly also immunomodulatory or even immunosuppressive, components. Thus, other approaches have been focussing on recombinant antigens,
which allow researchers to work with defined subsets of proteins that represent interesting targets. Most of the research on Neospora vaccines has been carried out employing murine models of cerebral infection (acute disease model) or models of foetal infection during pregnancy. One group of proteins/targets that is of interest for the development Kinase Inhibitor Library of a N. caninum vaccine are proteins that are secreted by the parasite at the onset of host cell adhesion and/or invasion. By targeting such molecules, one could possibly interfere in the vital mechanisms that lead to increased replication of the parasite within infected tissues. One of these antigens,
recombinant NcPDI (recNcPDI) (a protein disulphide isomerase), is localized in the parasite micronemes and the parasite surface. This is related to a protein found in the endoplasmic reticulum, functioning as a chaperone by interacting with S–S bridges and/or thiol groups, thus ensuring proper protein folding. Recombinant NcPDI was earlier shown to be involved in interactions between N. caninum either tachyzoites and host cells (15) and represents a target for thiazolide drugs, which have a profound impact on N. caninum tachyzoites (16–18). Subsequently, Debache et al. (19) found that vaccination with recNcPDI protected mice from cerebral infection by experimental N. caninum infection when applied intranasally, but not when applied intraperitoneally. We have here exploited these unusual features of recNcPDI and used this protein as a model antigen to investigate its properties whether delivered entrapped in a nanosized delivery system, consisting of chitosan-based nanogels surface decorated with alginate or alginate-mannose. Chitosan, a copolymer of d-glucosamine and N-acetyl-d-glucosamine is a derivative of chitin, one of the most abundant polysaccharides in nature.