A POLYGENTM-adjuvanted killed Neospora caninum tachyzoite preparation failed to prevent foetal infection in pregnant cattle following i.v./i.m. experimental tachyzoite challenge

Andrianarivo, A. G.; Rowe, Joan D; Barr, Bradd C.; Anderson, Margaret Lavinia; Packham, Andrea E.; Sverlow, Karen W.; Choromanski, Leszek; Loui, C.; Grace, Angelica; Conrad, Patricia A.

doi:10.1016/s0020-7519(00)00088-6

Cited by 67 publications

(39 citation statements)

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“…Our results are consistent with previous studies showing a predominant IgG1 response in calves orally infected with N. caninum oocysts [25], heifers inoculated with N. caninum tachyzoites by seminal infection [6], and pregnant cows intravenously-intramuscularly inoculated with N. caninum tachyzoites [29]. The lack of correlation between IgG titres and IFN-g levels has been reported in experimentally infected cattle [4,29,30], suggesting that factors other than IFN-g regulate IgG antibody production in cattle. This is the first study to report the presence of N. caninum DNA in the semen of experimentally infected bulls.…”

Section: Discussionsupporting

confidence: 92%

Experimental neosporosis in bulls: Parasite detection in semen and blood and specific antibody and interferon-gamma responses

et al. 2007

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Aim: To investigate the presence of Neospora caninum in semen and blood, and the development of specific antibody and interferon-gamma (IFN-g) responses in experimentally infected bulls. Methods: Eight bulls were intravenously infected with 10 8 live N. caninum tachyzoites of NC-1 isolate. The presence of N. caninum in semen and blood was assessed using a nested-PCR procedure. PCR-positive semen samples were bioassayed using a BALB/c nu/nu mouse model. Specific anti-N. caninum antibody and IFN-g responses were also examined. In parallel, eight seronegative bulls were studied as non-infected controls. All bulls were monitored for 26 weeks. Results: All eight experimentally infected bulls showed N. caninum DNA in their semen and/or blood samples at some time during the course of the study. Parasite load in semen ranged from 0.1 to 14.5 parasites/ml (mean 6.0). N. caninum could not be detected in BALB/c nu/nu mice inoculated with PCR-positive semen samples. A significant increase in mean serum specific IgM antibody response to N. caninum was detected between 10 and 28 days post-infection (p.i.). Serum specific IgG, IgG1, and IgG2 antibody levels in experimentally infected bulls were significantly different after 21, 10, and 14 days p.i. as compared to controls, respectively. Specific anti-N. caninum IgG were detected in seminal plasma from infected bulls and values obtained were different from controls after 25 days p.i. Mean specific IFN-g responses in experimentally infected bulls were significantly higher than controls 3 days p.i. Conclusions: This is the first study to report the presence of N. caninum DNA in the semen and blood of experimentally infected bulls. Our observations indicate an intermittent presence of N. caninum in low numbers in semen and associated with chronic stage of the infection. This study is also the first to report the detection of anti-N. caninum IgG in seminal plasma of experimentally infected bulls. #

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Section: Discussionsupporting

confidence: 92%

Experimental neosporosis in bulls: Parasite detection in semen and blood and specific antibody and interferon-gamma responses

et al. 2007

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“…To date, the main mode of control of neosporosis is based upon culling persistently infected, seropositive reproducing (Andrianarivo et al 2000;Innes and Vermeulen 2006). Toltrazuril is one of those few compounds that have demonstrated antiparasitic activity against N. caninum infections not only in cell culture-based assays, but also in vivo as shown in experimentally infected mice and even cattle (Darius et al 2004a, b;Gottstein et al 2001;Gottstein et al 2005;Kritzner et al 2002;Härdi et al 2006).…”

Section: Discussionmentioning

confidence: 99%

“…Although there are successful experimental vaccination approaches to prevent cerebral neosporosis (Cannas et al 2003a, b;Debache et al 2008) or vertical transmission (Nishikawa et al 2001) in mice, there are currently no vaccines available to protect cattle from abortion (Andrianarivo et al 2000;Innes and Vermeulen 2006).…”

Section: Introductionmentioning

confidence: 99%

Toltrazuril treatment of congenitally acquired Neospora caninum infection in newborn mice

et al. 2009

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C57BL/6 mice were infected with Neospora caninum tachyzoites during pregnancy, yielding a transplacental infection of developing fetuses. Subsequently, congenitally infected newborn mice were treated either once or three times with toltrazuril (or placebo) at a concentration of 31.25 mg compound per kg body weight. Both toltrazuril and placebo treatment had no negative effect on newborns, as noninfected treated pups developed normally without differences in mortality and morbidity to matching nontreated control animals. Already one application of toltrazuril was significantly (p<0.01) able to delay the outbreak of neosporosis in newborn mice, when compared to placebotreated infected controls. We found significantly higher proportion of surviving newborns in one-time-toltrazuriltreated and three-time-toltrazuril-treated groups (34% and 54%, respectively) when compared to one-time-placebotreated and three-time-placebo-treated groups (14% and 30%, respectively). There was no significant difference (p= 0.2) in the proportion of surviving pups between one-timetoltrazuril and three-time-toltrazuril treatment. However, the number of diseased and Neospora-positive pups (46% and 47%, respectively) was markedly reduced after three-timetoltrazuril treatment compared to all other groups. Threetime-treatment also resulted in the highest antibody (IgG, IgG2a) response. Pharmacokinetic analyses using individual serum samples revealed that, although toltrazuril was absorbed and metabolized to toltrazuril sulfone by newborn mice, medicated animals exhibited an unexpected rapid turnover (half-life time) of the compound. Toltrazuril and the metabolite were also found in brain tissues, indicating that passage of the blood-brain barrier occurred. In conclusion, we could show that three times treatment with toltrazuril had a high impact on the course of infection in congenitally N. caninum-infected newborn mice.

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“…Immunogens containing killed N. caninum tachyzoites do not protect against fetal infection in challenged cattle (1), and a whole-antigen immunogen exacerbated encephalitis in a mouse model of neosporosis (6), highlighting a need to identify specific protection-inducing antigens. Advantages to the epitope approach of vaccine development can include induction of more-potent responses, increased qualitative control of the immune response, targeting of dominant and subdominant epitopes, and overcoming of safety concerns regarding attenuated whole-organism preparations (46).…”

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confidence: 99%

Identification of Vaccine Candidate Peptides in the NcSRS2 Surface Protein ofNeospora caninumby Using CD4⁺Cytotoxic T Lymphocytes and Gamma Interferon-Secreting T Lymphocytes of Infected Holstein Cattle

et al. 2005

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Previously, our laboratory showed that Holstein cattle experimentally infected with Neospora caninum develop parasite-specific CD4 ؉ cytotoxic T lymphocytes (CTL) that lyse infected, autologous target cells through a perforin-granzyme pathway. To identify specific parasite antigens inducing bovine CTL and helper T-lymphocyte responses for vaccine development against bovine neosporosis, the tachyzoite major surface proteins NcSAG1 and NcSRS2 were targeted. In whole tachyzoite antigen-expanded bovine T-lymphocyte lines, recombinant NcSRS2 induced potent memory CD4؉ -and CD8 ؉ -T-lymphocyte activation, as indicated by proliferation and gamma interferon (IFN-␥) secretion, while recombinant NcSAG1 induced a minimal memory response. Subsequently, T-lymphocyte epitope-bearing peptides of NcSRS2 were mapped by using overlapping peptides covering the entire NcSRS2 sequence. Neospora caninum is an intracellular apicomplexan protozoan parasite that causes abortion and congenital infection in cattle (21). Transplacental parasite transmission is the major mode of infection (18, 45) which persists in the herd over successive generations, causing significant economic losses due to abortion, culling, and decreased milk production (13,20,25,52,53). Recrudescence of chronic, congenitally acquired infection due to downregulation of Th1 immune responses during pregnancy may be largely responsible for transplacental N. caninum transmission (10,22,27,42). A vaccine that could control tachyzoite parasitemia and decrease congenital infection or abortion rates is needed.Studies of Toxoplasma gondii, a protozoan parasite closely related to N. caninum in biology, phylogeny, and immunogenicity, unequivocally show the importance of T lymphocytes in resistance to infection by adoptive transfer, gene knockout, and depletion studies with mouse models (19). The presence of parasite-specific CD4 ϩ and CD8 ϩ cytotoxic T lymphocytes (CTL) is also associated with immunity to natural T. gondii infection in humans (14,41). In murine models of neosporosis, a T-lymphocyte-mediated immune response, characterized by increased levels of gamma interferon (IFN-␥) and interleukin 12 (IL-12), correlates with disease resistance (5,30,33), and IFN-␥ alone inhibits tachyzoite growth and cellular invasion (24,38,51,55). In pregnant mice, protection against vertical transmission correlates with induction of parasite-specific Tlymphocyte-mediated immunity (39). Cattle infected with N. caninum produce parasite-specific, major histocompatibility complex (MHC)-restricted, CD4 ϩ CTL (50) that could reduce N. caninum infection indirectly by IFN-␥ activation of mononuclear phagocytes and directly by killing N. caninum-infected cells.To identify vaccine candidate parasite antigens for induction of CTL and IFN-␥ secretion in cattle against neosporosis abortion, this study focused on major tachyzoite glycosylphosphatidylinositol-anchored surface proteins, N. caninum surface antigen 1 (NcSAG1) and N. caninum SAG1-related sequence 2 (NcSRS2) (26, 28). The T. gondii surface pr...

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A POLYGENTM-adjuvanted killed Neospora caninum tachyzoite preparation failed to prevent foetal infection in pregnant cattle following i.v./i.m. experimental tachyzoite challenge

Cited by 67 publications

References 22 publications

Experimental neosporosis in bulls: Parasite detection in semen and blood and specific antibody and interferon-gamma responses

Experimental neosporosis in bulls: Parasite detection in semen and blood and specific antibody and interferon-gamma responses

Toltrazuril treatment of congenitally acquired Neospora caninum infection in newborn mice

Identification of Vaccine Candidate Peptides in the NcSRS2 Surface Protein ofNeospora caninumby Using CD4⁺Cytotoxic T Lymphocytes and Gamma Interferon-Secreting T Lymphocytes of Infected Holstein Cattle

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A POLYGENTM-adjuvanted killed Neospora caninum tachyzoite preparation failed to prevent foetal infection in pregnant cattle following i.v./i.m. experimental tachyzoite challenge

Cited by 67 publications

References 22 publications

Experimental neosporosis in bulls: Parasite detection in semen and blood and specific antibody and interferon-gamma responses

Experimental neosporosis in bulls: Parasite detection in semen and blood and specific antibody and interferon-gamma responses

Toltrazuril treatment of congenitally acquired Neospora caninum infection in newborn mice

Identification of Vaccine Candidate Peptides in the NcSRS2 Surface Protein ofNeospora caninumby Using CD4+Cytotoxic T Lymphocytes and Gamma Interferon-Secreting T Lymphocytes of Infected Holstein Cattle

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Identification of Vaccine Candidate Peptides in the NcSRS2 Surface Protein ofNeospora caninumby Using CD4⁺Cytotoxic T Lymphocytes and Gamma Interferon-Secreting T Lymphocytes of Infected Holstein Cattle