scholarly journals Vaccination with Neospora GRA6 Interrupts the Vertical Transmission and Partially Protects Dams and Offspring against Neospora caninum Infection in Mice

Vaccines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 155
Author(s):  
Ragab M. Fereig ◽  
Hanan H. Abdelbaky ◽  
Yoshifumi Nishikawa
Keyword(s):  
Vertical Transmission ◽  
Neospora Caninum ◽  
Protective Efficacy ◽  
Parasite Burden ◽  
Clinical Score ◽  
Pregnant Mouse ◽  
Dense Granule ◽  
Economic Losses ◽  
Caninum Infection ◽  
Preventative Measures

Vaccination is the mainstay of preventative measures for numerous infectious diseases. Neospora caninum infection induces storms of abortion in pregnant cows and ewes, resulting in drastic economic losses because of fetal losses and culling of the dams. Herein, we evaluated the potential of recombinant protein of N. caninum dense granule protein 6 fused with glutathione-S-transferase (NcGRA6+GST) as a vaccine candidate against neosporosis in a pregnant mouse model. The protective efficacy was investigated by subcutaneous inoculation of BALB/c mice with recombinant NcGRA6+GST (25 pmol), and GST alone (25 pmol) or phosphate-buffered saline (PBS) as the controls. This study revealed the partial ability of NcGRA6+GST to protect the dams and offspring from N. caninum infection during the critical period of pregnancy. This ability was revealed by higher survival rate and lower parasite burden in brains of offspring of the NcGRA6+GST-immunized group in comparison with the control groups. In addition, mouse dams from NcGRA6+GST-immunized groups exhibited lower clinical score and minimum alteration in body weight in comparison with PBS or GST groups after challenge with N. caninum tachyzoites. Taken together, our results suggest the efficacy of recombinant NcGRA6 for interrupting the vertical transmission of N. caninum in mice by reducing the severity of infections in dams and offspring.

scholarly journals Immune Protective Evaluation Elicited by DNA Vaccination With Neospora caninum Dense Granules Proteins in Mice

2021 ◽  
Vol 8 ◽  
Author(s):  
Guili Yu ◽  
Wei Liang ◽  
Qiankun Yang ◽  
Jinxin Wang ◽  
Yu Wang ◽  
...  
Keyword(s):  
Survival Time ◽  
Dna Vaccines ◽  
Neospora Caninum ◽  
Protective Efficacy ◽  
Parasitophorous Vacuole ◽  
Parasite Burden ◽  
Economic Losses ◽  
Control Group ◽  
Dense Granules ◽  
Genes Encoding

Neospora caninum, an obligate intracellular protozoan, is the major cause for neosporosis and brings serious economic losses to cattle breeding industries worldwide. After invasion, dense granules proteins are abundantly secreted and being important components of parasitophorous vacuole and intravacuolar network where N. caninum survives and replicates. The aim of the present study was to evaluate the protective immunity induced by DNA vaccines with genes encoding dense granules proteins 1 (GRA1), GRA4, GRA9, GRA14, GRA17, and GRA23 against N. caninum tachyzoites in BALB/C mice. Eukaryotic expressing plasmids of pcNcGRAs were constructed and the mice were intramuscularly immunized with pcNcGRAs followed by challenging infection with lethal doses of N. caninum. Immune responses were evaluated through monitoring the levels of serum antibodies, measurement of lymphocyte proliferation, and secretion of cytokines. Immune protection assays were carried out through monitoring survival time, body weight, and parasite burden in the brains. Results showed that all the pcNcGRA DNA vaccines could trigger remarkably specific humoral and cellular responses, with higher levels of IgG and IgG2a antibodies as well as obviously increased secretion of Th1-type IFN-γ cytokines. The immune protective efficacy revealed that pcNcGRA4, pcNcGRA14, and pcNcGRA17 DNA vaccines could individually increase the survival rate to 50, 37.5, and 25% in comparison with 0% in the control group; prolong the survival time more than 20.88 ± 11.12, 18.88 ± 10.83, and 16.63 ± 10.66 days compared with the control group of 4 ± 1.31 days; and decrease parasite burden in the brains to 297.63 ± 83.77, 471.5 ± 110.74, and 592.13 ± 102.2 parasites/100 ng comparing with 1221.36 ± 269.59 parasites/100 ng in the control group. These findings indicated that NcGRA4, NcGRA14, and NcGRA17 are potential vaccine candidates; NcGRA4 displayed better performance in immune protective efficacy and could be further combined with other advantageous antigens applied to the development of safe and effective DNA vaccines against N. caninum.

Characterization of an Outbred Pregnant Mouse Model of Neospora caninum Infection

2002 ◽  
Vol 88 (4) ◽  
pp. 691
Author(s):  
Helen E. Quinn ◽  
Catherine M. D. Miller ◽  
Cheryl Ryce ◽  
Peter A. Windsor ◽  
John T. Ellis
Keyword(s):  
Mouse Model ◽  
Neospora Caninum ◽  
Pregnant Mouse ◽  
Caninum Infection

CHARACTERIZATION OF AN OUTBRED PREGNANT MOUSE MODEL OF NEOSPORA CANINUM INFECTION

2002 ◽  
Vol 88 (4) ◽  
pp. 691-696 ◽  
Author(s):  
Helen E. Quinn ◽  
Catherine M. D. Miller ◽  
Cheryl Ryce ◽  
Peter A. Windsor ◽  
John T. Ellis
Keyword(s):  
Mouse Model ◽  
Neospora Caninum ◽  
Pregnant Mouse ◽  
Caninum Infection

scholarly journals Protective Immunity Against Neospora Caninum Infection Induced by 14-3-3 Protein in Mice

2020 ◽  
Author(s):  
Shan Li ◽  
Nan Zhang ◽  
Shaoxiong Liu ◽  
Jianhua Li ◽  
Li Liu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vaccine Development ◽  
Neospora Caninum ◽  
Survival Rates ◽  
Parasite Burden ◽  
Mouse Serum ◽  
Intermediate Hosts ◽  
Caninum Infection ◽  
Wide Range ◽  
Ifn Γ

Abstract BackgroundNeospora caninum causes infections in a wide range of intermediate hosts and remains a threatening disease worldwide because of the lack of effective drugs and vaccines. Our previous studies demonstrated that N. caninum 14-3-3 protein (Nc14-3-3), which is included in N. caninum extracellular vesicles (NEVs), can induce effective immune responses and stimulate cytokine expression in mouse peritoneal macrophages. However, whether Nc14-3-3 has a protective effect and its mechanisms are poorly understood.MethodsHere, we evaluated immune responses and protective effects of Nc14-3-3 against 2×107 Nc-1 tachyzoites. Antibody (IgG, IgGl and IgG2a) levels and Th1-type (IFN-γ and IL-12) and Th2-type (IL-4 and IL-10) cytokines in mouse serum; survival rates; survival time; and parasite burdens were detected.ResultsIn the present study, the immunostimulatory effect of Nc14-3-3 was confirmed, as it triggered Th1-type cytokine (IFN-γ and IL-12) production in mouse serum two weeks after the final immunization. Moreover, the immunization of C57BL/6 mice with Nc14-3-3 induced high IgG antibody levels and significant increases in CD8+ T lymphocytes in the spleens of mice, indicating that a significant cellular immune response was induced. Mouse survival rates and survival times were significantly prolonged after immunization survival rates were 40% for Nc14-3-3 immunization and 60% for NEV immunization, while mice that received GST, PBS, or blank control all died at 13, 9, and 8 days after intraperitoneal N. caninum challenge. In addition, qPCR analysis indicated that there was a lower parasite burden and milder pathological changes in the mice immunized with Nc14-3-3.ConclusionsOur data demonstrate the vaccination of mice with Nc14-3-3 elicits both cellular and humoural immune responses and provides partial protection against acute neosporosis. Thus, Nc14-3-3 could be an effective antigen candidate for vaccine development for neosporosis.

scholarly journals Oral infection of neonate gerbils by Neospora caninum tachyzoites

2015 ◽  
Vol 46 (4) ◽  
pp. 654-659 ◽  
Author(s):  
Maiara Sanitá Tafner Ferreira ◽  
Fernanda Silveira Flores Vogel ◽  
Luis Antonio Sangioni ◽  
Augusto Weber ◽  
Patricia Bräunig ◽  
...  
Keyword(s):  
Neospora Caninum ◽  
Oral Route ◽  
Experimental Models ◽  
Meriones Unguiculatus ◽  
Economic Losses ◽  
Reproductive Disorders ◽  
Cattle Breeding ◽  
Caninum Infection ◽  
Oral Inoculation ◽  
Caninum Tachyzoites

ABSTRACT: Neosporosis is a parasitic disease caused by the protozoan Neospora caninum which results in major economic losses for cattle breeding due to abortion and other reproductive disorders. Gerbils (Meriones unguiculatus) are commonly used as experimental models for neosporosis due to their high susceptibility to N. caninum infection, both by oocysts ingestion as by tachyzoites/bradyzoites parenteral inoculation. However, the risk of transmission by tachyzoites ingestion is not fully elucidated. In this study, infection of neonate gerbils by N. caninum (NC-1 strain) tachyzoites inoculated by the oral route and the parasite distribution in gerbils' tissues were evaluated by protozoan DNA detection. Seventeen neonate gerbils, aged 4-5 days, were inoculated with 4x105 tachyzoites by the oral route and one gerbil was kept as uninfected control. N. caninum DNA was detected in 100% of the inoculated gerbils, showing that the oral route is effective as a potential route of infection of neonates by N. caninum tachyzoites. N. caninum DNA was reported in all organs evaluated (heart, lungs, kidneys, liver, spleen and brain), with different frequencies. These results showed systemically distributed infection of neonate gerbils after oral inoculation of tachyzoites.

scholarly journals Effects of Neospora caninum Infection at Mid-Gestation on Placenta in a Pregnant Mouse Model

2010 ◽  
Vol 96 (5) ◽  
pp. 1017-1020 ◽  
Author(s):  
I. C. López-Pérez ◽  
E. Collantes-Fernández ◽  
S. Rojo-Montejo ◽  
V. Navarro-Lozano ◽  
V. Risco-Castillo ◽  
...  
Keyword(s):  
Mouse Model ◽  
Neospora Caninum ◽  
Pregnant Mouse ◽  
Caninum Infection

scholarly journals Protective Immunity Against Neospora caninum Infection Induced by 14-3-3 Protein in Mice

2021 ◽  
Vol 8 ◽  
Author(s):  
Shan Li ◽  
Nan Zhang ◽  
Shaoxiong Liu ◽  
Jianhua Li ◽  
Li Liu ◽  
...  
Keyword(s):  
Immune Responses ◽  
Vaccine Development ◽  
Neospora Caninum ◽  
Survival Rates ◽  
Parasite Burden ◽  
Mouse Serum ◽  
Protective Effects ◽  
Igg Antibody ◽  
Caninum Infection ◽  
Ifn Γ

Neospora caninum is an apicomplexan parasite that infects many mammals and remains a threatening disease worldwide because of the lack of effective drugs and vaccines. Our previous studies demonstrated that N. caninum 14-3-3 protein (Nc14-3-3), which is included in N. caninum extracellular vesicles (NEVs), can induce effective immune responses and stimulate cytokine expression in mouse peritoneal macrophages. However, whether Nc14-3-3 has a protective effect and its mechanisms are poorly understood. Here, we evaluated the immune responses and protective effects of Nc14-3-3 against exposure to 2 × 107 Nc-1 tachyzoites. Antibody (IgG, IgGl, and IgG2a) levels and Th1-type (IFN-γ and IL-12) and Th2-type (IL-4 and IL-10) cytokines in mouse serum, survival rates, survival times, and parasite burdens were detected. In the present study, the immunostimulatory effect of Nc14-3-3 was confirmed, as it triggered Th1-type cytokine (IFN-γ and IL-12) production in mouse serum 2 weeks after the final immunization. Moreover, the immunization of C57BL/6 mice with Nc14-3-3 induced high IgG antibody levels and significant increases in CD8+ T lymphocytes in the spleens of mice, indicating that the cellular immune response was significantly stimulated. Mouse survival rates and times were significantly prolonged after immunization; the survival rates were 40% for Nc14-3-3 immunization and 60% for NEV immunization, while mice that received GST, PBS, or blank control all died at 13, 9, or 8 days, respectively, after intraperitoneal N. caninum challenge. In addition, qPCR analysis indicated that there was a reduced parasite burden and diminished pathological changes in the mice immunized with Nc14-3-3. Our data demonstrate that vaccination of mice with Nc14-3-3 elicits both cellular and humoral immune responses and provides partial protection against acute neosporosis. Thus, Nc14-3-3 could be an effective antigen candidate for vaccine development for neosporosis.

scholarly journals Transplacental transmission of Neospora caninum in naturally infected small ruminants from northeastern Brazil

2017 ◽  
Vol 37 (9) ◽  
pp. 921-925 ◽  
Author(s):  
Annelise C.B.T. Nunes ◽  
Elise M. Yamasaki ◽  
Pomy C.P. Kim ◽  
Renata P.B. Melo ◽  
Müller Ribeiro-Andrade ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Vertical Transmission ◽  
Neospora Caninum ◽  
Small Ruminants ◽  
Northeastern Brazil ◽  
Transplacental Transmission ◽  
Caninum Infection ◽  
Causative Agents ◽  
History Of ◽  
Different Tissues

ABSTRACT: Toxoplasma gondii and Neospora caninum are causative agents of abortion in sheep and goats. Thus, the present study aimed to describe the transplacental transmission of these protozoans in small ruminants of northeastern Brazil. Seventeen fetuses (6 goats and 11 sheep) from farms with history of abortion were necropsied and samples were collected from different tissues (brain, liver, lung, kidney and heart). The samples were analyzed by PCR, histopathology (HP) and immunohistochemistry (IHC) to evaluate whether T. gondii and/or N. caninum infection were the cause of abortion. None of the samples was positive for T. gondii according to PCR and IHC results. Some brain, liver, lung, kidney and heart samples of goat fetuses were positive for N. caninum by PCR. In the histopathology, mild mononuclear infiltration and necrosis with calcification were observed in the liver and brain of one goat fetus, respectively, that also was positive for N. caninum by PCR and IHC. The results confirmed vertical transmission of N. caninum in naturally infected goats of northeastern, Brazil.

scholarly journals In VitroandIn VivoEffects of the Bumped Kinase Inhibitor 1294 in the Related Cyst-Forming Apicomplexans Toxoplasma gondii and Neospora caninum

2015 ◽  
Vol 59 (10) ◽  
pp. 6361-6374 ◽  
Author(s):  
Pablo Winzer ◽  
Joachim Müller ◽  
Adriana Aguado-Martínez ◽  
Mahbubur Rahman ◽  
Vreni Balmer ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Vertical Transmission ◽  
Kinase Inhibitor ◽  
Neospora Caninum ◽  
Antigen Expression ◽  
Pregnant Mouse ◽  
Content Type ◽  
Elevated Expression ◽  
Bumped Kinase Inhibitor

ABSTRACTWe report on thein vitroeffects of the bumped kinase inhibitor 1294 (BKI-1294) in cultures of virulentNeospora caninumisolates Nc-Liverpool (Nc-Liv) and Nc-Spain7 and in two strains ofToxoplasma gondii(RH and ME49), all grown in human foreskin fibroblasts. In these parasites, BKI-1294 acted with 50% inhibitory concentrations (IC50s) ranging from 20 nM (T. gondiiRH) to 360 nM (N. caninumNc-Liv), and exposure of intracellular stages to 1294 led to the nondisjunction of newly formed tachyzoites, resulting in the formation of multinucleated complexes similar to complexes previously observed in BKI-1294-treatedN. caninumbeta-galactosidase-expressing parasites. However, such complexes were not seen in a transgenicT. gondiistrain that expressed CDPK1 harboring a mutation (G to M) in the gatekeeper residue. InT. gondiiME49 andN. caninumNc-Liv, exposure of cultures to BKI-1294 resulted in the elevated expression of mRNA coding for the bradyzoite marker BAG1. Unlike in bradyzoites, SAG1 expression was not repressed. Immunofluorescence also showed that these multinucleated complexes expressed SAG1 and BAG1 and the monoclonal antibody CC2, which binds to a yet unidentified bradyzoite antigen, also exhibited increased labeling. In a pregnant mouse model, BKI-1294 efficiently inhibited vertical transmission in BALB/c mice experimentally infected with one of the two virulent isolates Nc-Liv or Nc-Spain7, demonstrating proof of concept that this compound protected offspring from vertical transmission and disease. The observed deregulated antigen expression effect may enhance the immune response during BKI-1294 therapy and will be the subject of future studies.

Low rates of Neospora caninum infection reactivation during gestation are observed in both chronically and congenitally infected mice

Parasitology ◽  
2012 ◽  
Vol 140 (2) ◽  
pp. 220-228 ◽  
Author(s):  
E. JIMÉNEZ-RUIZ ◽  
G. ÁLVAREZ-GARCíA ◽  
A. AGUADO-MARTÍNEZ ◽  
L. M. ORTEGA-MORA
Keyword(s):  
Vertical Transmission ◽  
First Generation ◽  
Neospora Caninum ◽  
Caninum Infection ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
High Virulence ◽  
Group 2 ◽  
First Time ◽  
Group 1

SUMMARYEndogenous transplacental transmission (EnTT) of Neospora caninum is the most common route of infection in cattle and occurs as a consequence of a reactivation of N. caninum infection that may lead to abortion or to the birth of congenitally infected calves. The reactivation of N. caninum infection was studied during the gestation of chronically infected dams and, for the first time, in their congenitally infected pups. BALB/c mice were infected with Nc-Spain 7 (Group 1) or Nc-Spain 3H (Group 2), high virulence isolates and low-to-moderate virulence isolates, respectively. The mice were mated after 90 days post-infection, and the morbidity, mortality, vertical transmission and humoral immune responses were recorded for 2 consecutive generations. In the first generation, higher morbidity and mortality rates were observed in G1 before mating than in G2 (P < 0·0001). In the second generation, low vertical transmission rates were observed in both inoculated groups (7·7% and 17·1% in G1 and G2, respectively) and were significantly diminished in the third generation (8·7% in G2 versus 0% in G1). Low rates of reactivation of N. caninum infection were induced in chronically infected mice and decreased in subsequent generations regardless of the isolate employed in the inoculations. Thus, further studies are needed to improve this reactivation mouse model.

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