This study was designed to identify changes in parasite-specific immune responses that occur during vertical transmission of Neospora caninum and can be used as indicators of parasite reactivation in naturally infected heifers. Ten heifers were unimmunized and 11 immunized with killed tachyzoites. One unimmunized heifer, which aborted at week 19 of gestation, had an increase in parasite-specific antibodies, mainly IgG(2), from week 15 to week 19 and a concomitant decline in parasite-specific cell-mediated immune (CMI) responses. Eight unimmunized heifers, which had live full-term congenitally infected calves, had an increase in antibodies, mainly IgG(2), from week 21 onwards. All immunized heifers delivered live full-term congenitally infected calves, and had a bimodal increase in antibodies; primarily IgG(1) following immunization and predominantly IgG(2) from week 17 onwards. Immunized heifers had significantly greater overall mean humoral and CMI responses than unimmunized heifers. Nine uninfected control heifers and their calves were seronegative. These results indicate that reactivation of a latent infection occurred in the naturally infected heifers, regardless of their immunization status, and was associated with increased parasite-specific antibodies, mainly IgG(2).
"It is well acknowledged in the literature that the development of vaccines directed against T. gondii and N. caninum should focus on selecting proteins that are capable of eliciting mainly a cell-mediated immune (CMI) response involving CD4 + ve T cells, Type 1 helper T cells (Th1) and Interferon-gamma (IFN-γ) in addition to a humoral response [19,41-43]. Seventy of the evidence profiles are for proteins from published studies. "
[Show abstract][Hide abstract] ABSTRACT: An in silico vaccine discovery pipeline for eukaryotic pathogens typically consists of several computational tools to predict protein characteristics. The aim of the in silico approach to discovering subunit vaccines is to use predicted characteristics to identify proteins which are worthy of laboratory investigation. A major challenge is that these predictions are inherent with hidden inaccuracies and contradictions. This study focuses on how to reduce the number of false candidates using machine learning algorithms rather than relying on expensive laboratory validation. Proteins from Toxoplasma gondii, Plasmodium sp., and Caenorhabditis elegans were used as training and test datasets.
The results show that machine learning algorithms can effectively distinguish expected true from expected false vaccine candidates (with an average sensitivity and specificity of 0.97 and 0.98 respectively), for proteins observed to induce immune responses experimentally.
Vaccine candidates from an in silico approach can only be truly validated in a laboratory. Given any in silico output and appropriate training data, the number of false candidates allocated for validation can be dramatically reduced using a pool of machine learning algorithms. This will ultimately save time and money in the laboratory.
"(Buxton, 1993; Bock et al., 2004; Shirley et al., 2005) encourages further research to develop a live vaccine to prevent bovine neosporosis. Many studies evaluating inactivated vaccine in cattle have been largely unsuccessful after experimental challenge (Andrianarivo et al., 1999, 2000; Williams et al., 2007) or in natural persistently infected cattle (Andrianarivo et al., 2005). Epidemiological data suggest that a low efficacy (<50%) could be achieved using a killed vaccine under field conditions varying from farm to farm (Romero et al., 2004; Weston et al., 2012). "
[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to evaluate whether Neospora caninum tachyzoites (Nc-1) inoculated by the conjunctival route in pregnant cows were able to generate infection in their fetuses. Group 1 contained 2 naturally infected cows; group 2 contained two cows inoculated intravenously with 2.5×10(8) tachyzoites, group 3 contained two cows inoculated with 2.5×10(8) tachyzoites by the conjunctival route, and group 4 contained two uninfected control cows. The four inoculated cows from groups 2 and 3 were challenged at 23 weeks of gestation. An indirect fluorescent antibody test (IFAT), recombinant NcGRA7-based ELISA, ELISA for IgG subisotypes and Western blot analysis were assessed to characterize the humoral immune response in dams. Sera from their fetuses were tested also using Western blot analysis. Routine microscopic evaluation of H&E stained fetal tissues was made and any fetal tissues and placentas with lesions compatible with Neospora-infection were processed by immunohistochemistry (IHC). DNA extraction from fresh and formalin-fixed, paraffin-embedded fetal tissues were tested by nested PCR. All dams from groups 1, 2 and 3 were seropositive by IFAT, rNcGRA7-based-ELISA and Western blot. IgG1/IgG2 ratios were ≤1 at weeks 27 and 29 of gestation. Only fetuses from groups 1 and 2 developed N. caninum specific antibodies by Western blot. Histopathological lesions compatible with those caused by N. caninum were observed in fetuses from groups 1 and 2. N. caninum cysts and tachyzoites were observed by IHC on fetal tissues from groups 1 and 2. Only fetal samples from group 2 were positive by PCR. Further work is needed not only to characterize the cellular immune response but also to clarify the consequences on the dam after conjunctival inoculation of N. caninum tachyzoites. This study shows that N. caninum tachyzoites inoculated by the conjunctival route were not vertically transmitted in pregnant cows.
"Neospora-specific cell mediated and innate immune responses are likely to be involved in protection against the parasite, in naturally  as well as experimentally infected animals [10,13,19,20]. Data from several studies has demonstrated that lymphocyte proliferation and interferon-γ (IFN-γ) responses are involved during an immune response to N. caninum[11,21-23], and that these responding immune cells tend to be CD4+ T lymphocytes [20,24,25]. "
[Show abstract][Hide abstract] ABSTRACT: This study examined the immunological responses of pregnant cattle and their foetuses following an experimental challenge with live Neospora caninum tachyzoites at day 210 of gestation. Animals were bled prior to and weekly throughout the experiment and sacrificed at 14, 28, 42 and 56 days post inoculation (dpi). At post mortem examination, samples of lymph nodes and spleen were collected from both dam and foetus for immunological analysis. Subcutaneous (sc) inoculation over the left prefemoral (LPF) lymph node of pregnant cattle at day 210 of gestation, led to the vertical transmission of parasites by 14 dpi, however no foetal deaths were observed in the infected animals. Foetuses from infected dams mounted Neospora-specific humoral and cell-mediated immune (CMI) responses by 14 dpi. These responses involved anti-Neospora IgG, antigen-specific lymphocyte proliferation, and the production of the cytokines IFN–γ, interleukin (IL)-4 and IL-10. There was also evidence of innate immunity during the response against Neospora from infected dams, with statistically significant (p < 0.05) increases in mean expression of toll like receptors (TLR)-2 on 56 dpi in maternal spleen, LPF, right prefemoral (RPF), left uterine (LUL) and right uterine (RUL) lymph nodes and TLR-9 in retropharyngeal (RLN), LPF and RPF lymph nodes from 28 dpi. Statistically significant (p < 0.05) increases in mean TLR-9 were detected in spleen samples from foetuses of infected dams, compared to the foetuses from control animals. Our results show that vertical transmission of the parasite occurred in all infected dams, with their foetuses showing effective Neospora-specific cell mediated, humoral and innate immune responses.
Veterinary Research 10/2013; 44(1):91. DOI:10.1186/1297-9716-44-91 · 2.82 Impact Factor
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