Low efficacy of NcGRA7, NcSAG4, NcBSR4 and NcSRS9 formulated in poly-ε-caprolactone against Neospora caninum infection in mice.
ABSTRACT The protective efficacy of vaccination with Neospora caninum recombinant antigens was evaluated in Balb/c pregnant and non-pregnant mouse models of neosporosis. A major immunodominant dense granule protein (NcGRA7) and three bradyzoite-specific surface antigens (NcSAG4, NcBSR4 and NcSRS9) were expressed in Escherichia coli and encapsulated within poly-ε-caprolactone (PCL) nanoparticles for the first time. Good efficiencies of entrapment (greater than 50%) were obtained for all encapsulated proteins. Moreover, antigenicity was unaffected after formulation. Afterwards, separate groups of mice were immunised with the nanoparticles and were then challenged with N. caninum tachyzoites. High IgG1 and IgG2a antibody levels of anti-N. caninum and specific antibodies directed against recombinant proteins were developed by all of the immunised groups. Mice previously inoculated with encapsulated rNcGRA7 produced significant levels of IFN-γ. However, in general, a low production of IFN-γ was detected. This may indicate a failure in the complete liberation of antigens after immunisation or an incorrect balance of the Th1/Th2 response to combat acute neosporosis during pregnancy. In fact, high morbidity and mortality rates were observed in dams. Moreover, vertical transmission was not prevented, and high neonatal mortality rates occurred similarly among the groups. Despite the global absence of efficacy, the study reveals some results of positive efficacy regarding dams and pups' survival and parasite presence for NcSRS9 recombinant protein. Furthermore, vaccination with rNcGRA7 encapsulated alone or combined with rNcSAG4 resulted in a slight decrease of parasite presence in non-pregnant mice. These promising results are further discussed to suggest new approaches that may be more suitable to test vaccine formulations based on bradyzoite stage-specific proteins.
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ABSTRACT: Neospora caninum is a protozoan parasite of animals. Until 1988, it was misdiagnosed as Toxoplasma gondii. Since its first recognition in 1984 in dogs and the description of a new genus and species Neospora caninum in 1988, neosporosis has emerged as a serious disease of cattle and dogs worldwide. Abortions and neonatal mortality are a major problem in livestock operations and neosporosis is a major cause of abortion in cattle. This review is focused on current status of neosporosis in animals based on papers published in the last five years. Worldwide seroprevalences are tabulated. Strategies for control and prevention are discussed.Veterinary Parasitology 05/2011; 180(1-2):90-108. · 2.58 Impact Factor
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ABSTRACT: Neospora caninum is a protozoan parasite of animals. Until 1988, it was misidentified as Toxoplasma gondii. Since its first recognition in dogs in 1984 and the description of the new genus and species Neospora caninum in 1988, neosporosis has emerged as a serious disease of cattle and dogs worldwide. Abortions and neonatal mortality are a major problem in livestock operations, and neosporosis is a major cause of abortion in cattle. Although antibodies to N. caninum have been reported, the parasite has not been detected in human tissues. Thus, the zoonotic potential is uncertain. This review is focused mainly on the epidemiology and control of neosporosis in cattle, but worldwide seroprevalences of N. caninum in animals and humans are tabulated. The role of wildlife in the life cycle of N. caninum and strategies for the control of neosporosis in cattle are discussed.Clinical Microbiology Reviews 05/2007; 20(2):323-67. · 16.13 Impact Factor
Article: Immunization of cattle with live tachyzoites of Neospora caninum confers protection against fetal death.[show abstract] [hide abstract]
ABSTRACT: Neospora caninum is an obligate intracellular protozoan parasite that causes abortion in cattle. It is normally found as a latent infection controlled by a T-helper-cell type 1 response involving CD4(+) cytotoxic T cells and gamma interferon. Cattle may be infected by two different routes: transplacentally as a result of activation of the latent infection in the mother causing congenital infection or abortion and by ingestion of oocysts, which, if it occurs during gestation, can also result in abortion. Here, for the first time, we establish proof that live vaccination protects against fetal death, whereas immunization using whole-tachyzoite lysate in different adjuvants fails to protect against fetal death. Strong antibody responses were induced in all the vaccinated groups, and the quality and magnitude of these responses were similar in the live- and the lysate-vaccinated groups. In contrast, only the group immunized with live tachyzoites had strong cellular and gamma interferon responses prior to challenge, and these responses correlated with protection against fetopathy. These results suggest that a cellular immune response may be important in the mechanisms involved in protection against N. caninum-associated abortions.Infection and Immunity 04/2007; 75(3):1343-8. · 4.16 Impact Factor