Vaccines and drugs against Neospora caninum, an important apicomplexan causing abortion in cattle and other farm animals

Abstract

Abstract:The apicomplexan parasite Neospora caninum represents an important abortioncausing parasite in cattle. The economic impact of neosporosis has led to considerable investments to develop vaccines that would prevent infection and abortion. Live-attenuated vaccines have been shown to confer some protection against N. caninum infection, but may cause problems due to regulatory issues and other drawbacks. Therefore, efforts have been undertaken to develop recombinant subunit vaccines based on antigens involved in adhesion/invasion or other parasite-host cell interaction processes. Concerning chemotherapeutical agents, the currently known arsenal of active drugs that act against N. caninum is limited to a small number of compounds with suitable in vitro properties including low inhibition constants, parasitocidal effects, and low cytotoxicity. For in vivo studies, mostly small laboratory animal models that mimic cerebral infection, acute disease, and fetal loss upon infection during pregnancy have been applied for the assessment of vaccines or drug candidates. However, only a small number of recombinant vaccines and drug candidates have met the expectations, and small laboratory models for neosporosis need to be standardized in order to be able to compare the results of different laboratories. Few vaccines and compounds have made it into trials involving ruminant models such as cattle or sheep, including live-attenuated vaccines and the anticoccidial drug toltrazuril. We here summarize the current status of vaccine and drug development for neosporosis.

Neospora caninum surface antigen 1 is a major determinant of the pathogenesis of neosporosis in nonpregnant and pregnant mice

“…Numerous previous studies have revealed the efficient potential of NcSAG1 in stimulating cellular or humoral immune responses [reviewed thoroughly by Hemphill and Müller (2015) ; Aguado-Martinez et al (2017) ; Sinnott et al (2017) ; Fereig and Nishikawa (2020) ]. However, the immunomodulatory effect of NcSAG1 is more likely relevant to the cellular than the humoral immune response ( Kato et al, 2015 ; Marin et al, 2017 ).…”

Annotating the ‘hypothetical’ in hypothetical proteins: In-silico analysis of uncharacterised proteins for the Apicomplexan parasite, Neospora caninum

“…While it is logical to assume that essential protein-coding genes implicated in parasite virulence have been identified, the sheer number of unclassified or hypothetical regions cannot be neglected or deemed unimportant, prompting this study. Current vaccine candidates for parasites within this phylum involve either surface or secreted antigens that appear to be fundamental to parasite invasion, the mechanisms and contributors of which appear to be mostly conserved (Kim and Weiss, 2004;Hemphill, 2015). Consequently, the identification and investigation of uncharacterised proteins through sequence homology, structure, and known hallmarks of parasite virulence, has the power to perpetuate the discovery of targets for vaccine development.…”