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 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 Immediate Interferon Gamma Induction Determines Murine Host Compatibility Differences between Toxoplasma gondii and Neospora caninum

2020 ◽  
Vol 88 (4) ◽  
Author(s):  
Rachel S. Coombs ◽  
Matthew L. Blank ◽  
Elizabeth D. English ◽  
Yaw Adomako-Ankomah ◽  
Ifeanyi-Chukwu Samuel Urama ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Immune Responses ◽  
Interferon Gamma ◽  
Neospora Caninum ◽  
Ectopic Expression ◽  
Parasite Burden ◽  
Interleukin 12 ◽  
Content Type ◽  
Ifn Γ ◽  
And Control

ABSTRACT Rodents are critical for the transmission of Toxoplasma gondii to the definitive feline host via predation, and this relationship has been extensively studied as a model for immune responses to parasites. Neospora caninum is a closely related coccidian parasite of ruminants and canines but is not naturally transmitted by rodents. We compared mouse innate immune responses to N. caninum and T. gondii and found marked differences in cytokine levels and parasite growth kinetics during the first 24 h postinfection (hpi). N. caninum-infected mice produced significantly higher levels of interleukin-12 (IL-12) and interferon gamma (IFN-γ) by as early as 4 hpi, but the level of IFN-γ was significantly lower or undetectable in T. gondii-infected mice during the first 24 hpi. “Immediate” IFN-γ and IL-12p40 production was not detected in MyD88−/− mice. However, unlike IL-12p40−/− and IFN-γ−/− mice, MyD88−/− mice survived N. caninum infections at the dose used in this study. Serial measures of parasite burden showed that MyD88−/− mice were more susceptible to N. caninum infections than wild-type (WT) mice, and control of parasite burdens correlated with a pulse of serum IFN-γ at 3 to 4 days postinfection in the absence of detectable IL-12. Immediate IFN-γ was partially dependent on the T. gondii mouse profilin receptor Toll-like receptor 11 (TLR11), but the ectopic expression of N. caninum profilin in T. gondii had no impact on early IFN-γ production or parasite proliferation. Our data indicate that T. gondii is capable of evading host detection during the first hours after infection, while N. caninum is not, and this is likely due to the early MyD88-dependent recognition of ligands other than profilin.

scholarly journals Protection against Lethal Neospora caninum Infection in Mice Induced by Heterologous Vaccination with a mic1 mic3 Knockout Toxoplasma gondii Strain

2009 ◽  
Vol 78 (2) ◽  
pp. 651-660 ◽  
Author(s):  
Diana Marcela Penarete-Vargas ◽  
Marie Noelle Mévélec ◽  
Sarah Dion ◽  
Edouard Sèche ◽  
Isabelle Dimier-Poisson ◽  
...  
Keyword(s):  
Toxoplasma Gondii ◽  
Neospora Caninum ◽  
Survival Rates ◽  
Congenital Toxoplasmosis ◽  
Neonatal Morbidity ◽  
Caninum Infection ◽  
Obligate Intracellular ◽  
Intracellular Parasites ◽  
Wide Range ◽  
Vertebrate Hosts

ABSTRACT Neospora caninum and Toxoplasma gondii are closely related, obligate intracellular parasites infecting a wide range of vertebrate hosts and causing abortion and neonatal morbidity and mortality. Several lines of evidence suggest that cross immunity between these two pathogens could be exploited in the design of strategies for heterologous vaccination. We assessed the ability of an attenuated strain of T. gondii (“mic1-3KO strain”) conferring strong protection against chronic and congenital toxoplasmosis to protect mice against lethal N. caninum infection. Mice immunized with mic1-3KO tachyzoites by the oral and intraperitoneal routes developed a strong cellular Th1 response and displayed significant protection against lethal heterologous N. caninum infection, with survival rates of 70% and 80%, respectively, whereas only 30% of the nonimmunized mice survived. We report here the acquisition of heterologous protective immunity against N. caninum following immunization with a live attenuated mic1-3KO strain of T. gondii.

scholarly journals TLR3-TRIF pathway activation by Neospora caninum RNA enhances infection control

2018 ◽  
Author(s):  
Vanessa dos Santos Miranda ◽  
Flávia Batista Ferreira França ◽  
Mylla Spirandelli da Costa ◽  
Vanessa Resende Souza Silva ◽  
Caroline Martins Mota ◽  
...  
Keyword(s):  
Immune Responses ◽  
Neospora Caninum ◽  
Parasitophorous Vacuole ◽  
Parasite Burden ◽  
Protozoan Parasite ◽  
Economic Losses ◽  
Pathway Activation ◽  
Ifn Γ ◽  
Th1 Immune Responses

AbstractNeospora caninum is a protozoan parasite closely related to Toxoplasma gondii and has been studied for causing neuromuscular disease in dogs and abortions in cattle. It is recognized as the major cause of economic losses in bovine products. In that sense, this study aimed to evaluate the role of TLR3-TRIF dependent resistance against N. caninum infection. We observed that TLR3−/− and TRIF−/− mice presented higher parasite burden, increased inflammatory lesions and reduced production of IL-12p40, TNF, IFN-γ, and NO. Differently from T. gondii, N. caninum tachyzoites and its RNA recruited TLR3 and IRF3 to the parasitophorous vacuole (PV). We observed that N. caninum upregulated the expression of TRIF in macrophages, which by its turn upregulated IFN-α and IFN-β in the presence of the parasite. Furthermore, TRIF−/− infected macrophages produced lower levels of IL-12p40 and IFN-α replacement was able to completely restore the production of this key cytokine. Our results have shown that TLR3-TRIF signaling pathway enhances resistance against N. caninum infection, since it improves Th1 immune responses that control parasitism and tissue inflammation, which are hallmarks of the disease.

scholarly journals Neospora caninuminfection in birds: experimental infections in chicken and embryonated eggs

Parasitology ◽  
2007 ◽  
Vol 134 (14) ◽  
pp. 1931-1939 ◽  
Author(s):  
P. I. FURUTA ◽  
T. W. P. MINEO ◽  
A. O. T. CARRASCO ◽  
G. S. GODOY ◽  
A. A. PINTO ◽  
...  
Keyword(s):  
Laying Hens ◽  
Neospora Caninum ◽  
Parasite Burden ◽  
Asymptomatic Infection ◽  
Igg Antibodies ◽  
Intermediate Hosts ◽  
Susceptibility To Infection ◽  
Experimental Infections ◽  
Inoculum Dose ◽  
Specific Igg

SUMMARYNeospora caninumcauses economical impact in cattle-raising farms since it is implicated as the major cause of bovine abortions. Although infection by the parasite has been widely described in mammals, the role of birds in its life-cycle is still obscure. Therefore, this work aimed to evaluate the infection byN. caninumin different chicken models. Experimental infections were conducted in 7-day-old chicks, laying hens and embryonated eggs, where samples were analysed for parasite burden, IgG antibodies and lesions promoted. Chickens demonstrated an asymptomatic infection, although with seroconversion and systemic replication of the parasite. In laying hens, no signs of vertical transmission were observed. However, embryonated eggs inoculated by the allantoic cavity route demonstrated susceptibility to infection, with mortality rates around 50% independent of the inoculum dose. Additionally, dogs became infected after ingestion of different amounts of inoculated eggs, producing either oocysts or specific IgG antibodies. The results herein presented demonstrate that chickens may be intermediate hosts ofN. caninumand that embryonated eggs could be a useful model to study the parasite's biology.

scholarly journals Treatment of Toxoplasmosis and Neosporosis in Farm Ruminants: State of Knowledge and Future Trends

2018 ◽  
Vol 18 (15) ◽  
pp. 1304-1323 ◽  
Author(s):  
Roberto Sánchez-Sánchez ◽  
Patricia Vázquez ◽  
Ignacio Ferre ◽  
Luis Miguel Ortega-Mora
Keyword(s):  
Vaccine Development ◽  
Neospora Caninum ◽  
Treatment Options ◽  
Small Ruminants ◽  
Additional Treatment ◽  
Current Status ◽  
Caninum Infection ◽  
Zoonotic Parasites ◽  
Toxoplasma Gondii Infection

Toxoplasmosis and neosporosis are closely related protozoan diseases that lead to important economic impacts in farm ruminants. Toxoplasma gondii infection mainly causes reproductive failure in small ruminants and is a widespread zoonosis, whereas Neospora caninum infection is one of the most important causes of abortion in cattle worldwide. Vaccination has been considered the most economic measure for controlling these diseases. However, despite vaccine development efforts, only a liveattenuated T. gondii vaccine has been licensed for veterinary use, and no promising vaccines against neosporosis have been developed; therefore, vaccine development remains a key goal. Additionally, drug therapy could be a valuable strategy for disease control in farm ruminants, as several drugs that limit T. gondii and N. caninum proliferation and dissemination have been evaluated. This approach may also be relevant to performing an initial drug screening for potential human therapy for zoonotic parasites. Treatments can be applied against infections in adult ruminants to minimize the outcomes of a primo-infection or the reactivation of a chronic infection during gestation or in newborn ruminants to avoid infection chronification. In this review, the current status of drug development against toxoplasmosis and neosporosis in farm ruminants is presented, and in an effort to promote additional treatment options, prospective drugs that have shown efficacy in vitro and in laboratory animal models of toxoplasmosis and neosporosis are examined.

scholarly journals Recent Advances in Nanovaccines Using Biomimetic Immunomodulatory Materials

Pharmaceutics ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 534 ◽  
Author(s):  
Vijayan ◽  
Mohapatra ◽  
Uthaman ◽  
Park
Keyword(s):  
Immune Responses ◽  
Targeted Delivery ◽  
Vaccine Development ◽  
Polymeric Nanoparticles ◽  
Vital Role ◽  
Effective Control ◽  
Therapeutic Vaccines ◽  
Hiv Therapy ◽  
Recent Advances ◽  
Wide Range

The development of vaccines plays a vital role in the effective control of several fatal diseases. However, effective prophylactic and therapeutic vaccines have yet to be developed for completely curing deadly diseases, such as cancer, malaria, HIV, and serious microbial infections. Thus, suitable vaccine candidates need to be designed to elicit appropriate immune responses. Nanotechnology has been found to play a unique role in the design of vaccines, providing them with enhanced specificity and potency. Nano-scaled materials, such as virus-like particles, liposomes, polymeric nanoparticles (NPs), and protein NPs, have received considerable attention over the past decade as potential carriers for the delivery of vaccine antigens and adjuvants, due to their beneficial advantages, like improved antigen stability, targeted delivery, and long-time release, for which antigens/adjuvants are either encapsulated within, or decorated on, the NP surface. Flexibility in the design of nanomedicine allows for the programming of immune responses, thereby addressing the many challenges encountered in vaccine development. Biomimetic NPs have emerged as innovative natural mimicking biosystems that can be used for a wide range of biomedical applications. In this review, we discuss the recent advances in biomimetic nanovaccines, and their use in anti-bacterial therapy, anti-HIV therapy, anti-malarial therapy, anti-melittin therapy, and anti-tumor immunity.

scholarly journals Vaccination with Lentiviral Vector Expressing thenfa1Gene Confers a Protective Immune Response to Mice Infected with Naegleria fowleri

2013 ◽  
Vol 20 (7) ◽  
pp. 1055-1060 ◽  
Author(s):  
Jong-Hyun Kim ◽  
Hae-Jin Sohn ◽  
Jinyoung Lee ◽  
Hee-Jong Yang ◽  
Yong-Joon Chwae ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Viral Vector ◽  
Lentiviral Vector ◽  
Survival Rates ◽  
Dna Vaccination ◽  
Naegleria Fowleri ◽  
Content Type ◽  
Ifn Γ ◽  
Nægleria Fowleri

ABSTRACTNaegleria fowleri, a pathogenic free-living amoeba, causes fatal primary amoebic meningoencephalitis (PAM) in humans and animals. Thenfa1gene (360 bp), cloned from a cDNA library ofN. fowleri, produces a 13.1-kDa recombinant protein which is located on pseudopodia, particularly the food cup structure. Thenfa1gene plays an important role in the pathogenesis ofN. fowleriinfection. To examine the effect ofnfa1DNA vaccination againstN. fowleriinfection, we constructed a lentiviral vector (pCDH) expressing thenfa1gene. For thein vivomouse study, BALB/c mice were intranasally vaccinated with viral particles of a viral vector expressing thenfa1gene. To evaluate the effect of vaccination and immune responses of mice, we analyzed the IgG levels (IgG, IgG1, and IgG2a), cytokine induction (interleukin-4 [IL-4] and gamma interferon [IFN-γ]), and survival rates of mice that developed PAM. The levels of both IgG and IgG subclasses (IgG1 and IgG2a) in vaccinated mice were significantly increased. The cytokine analysis showed that vaccinated mice exhibited greater IL-4 and IFN-γ production than the other control groups, suggesting a Th1/Th2 mixed-type immune response. In vaccinated mice, high levels of Nfa1-specific IgG antibodies continued until 12 weeks postvaccination. The mice vaccinated with viral vector expressing thenfa1gene also exhibited significantly higher survival rates (90%) after challenge withN. fowleritrophozoites. Finally, thenfa1vaccination effectively induced protective immunity by humoral and cellular immune responses inN. fowleri-infected mice. These results suggest that DNA vaccination using a viral vector may be a potential tool againstN. fowleriinfection.

scholarly journals Bovine Immune Response to Inoculation with Neospora caninum Surface Antigen SRS2 Lipopeptides Mimics Immune Response to Infection with Live Parasites

2008 ◽  
Vol 15 (4) ◽  
pp. 659-667 ◽  
Author(s):  
Timothy V. Baszler ◽  
Varda Shkap ◽  
Waithaka Mwangi ◽  
Christopher J. Davies ◽  
Bruce A. Mathison ◽  
...  
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Dna Vaccine ◽  
T Lymphocyte ◽  
Mononuclear Cells ◽  
Neospora Caninum ◽  
Lymphocyte Activation ◽  
T Lymphocyte Activation ◽  
T Lymphocyte Proliferation ◽  
Ifn Γ

ABSTRACT Infection of cattle with Neospora caninum protozoa, the causative agent of bovine protozoal abortion, results in robust cellular and humoral immune responses, particularly CD4+ T-lymphocyte activation and gamma interferon (IFN-γ) secretion. In the present study, N. caninum SRS2 (NcSRS2) T-lymphocyte-epitope-bearing subunits were incorporated into DNA and peptide preparations to assess CD4+ cell proliferation and IFN-γ T-lymphocyte-secretion immune responses in cattle with predetermined major histocompatibility complex (MHC) genotypes. In order to optimize dendritic-cell processing, NcSRS2 DNA vaccine was delivered with granulocyte macrophage-colony-stimulating factor and Flt3 ligand adjuvant. The synthesized NcSRS2 peptides were coupled with a palmitic acid molecule (lipopeptide) and delivered with Freund's adjuvant. Cattle vaccinated with NcSRS2 DNA vaccine alone did not induce T-lymphocyte activation or IFN-γ secretion, whereas subsequent booster inoculation with NcSRS2-lipopeptides induced robust NcSRS2-specific immune responses. Compared to the response in control animals, NcSRS2-lipopeptide-immunized cattle had significantly increased NcSRS2-specific T-lymphocyte proliferation, numbers of IFN-γ-secreting peripheral blood mononuclear cells, and immunoglobulin G1 (IgG1) and IgG2a antibody levels. The findings show that N. caninum NcSRS2 subunits bearing T-lymphocyte epitopes induced cell-mediated immune responses similar to the protective immune responses previously described against live parasite infection, namely T-lymphocyte activation and IFN-γ secretion. The findings support the investigation of NcSRS2 immunogens for protection against N. caninum-induced fetal infection and abortion in cattle.

scholarly journals Vaccine containing immunologic adjuvants with a wide range of activity to provide protection against COVID-19

2021 ◽  
Author(s):  
Mulugeta Berhanu
Keyword(s):  
Immune Responses ◽  
Immune Cells ◽  
Vaccine Development ◽  
Narrow Range ◽  
Wide Spectrum ◽  
Aluminum Salts ◽  
Global Problem ◽  
Wide Range ◽  
Immunologic Adjuvants

This paper proposes a wide spectrum immunologic adjuvant for vaccine development against  COVID-19 which is the current global problem. It has been reported that a wide range of immune cells are involved in the body’s response to SARS CoV2 infection. Therefore, vaccine with a wide-spectrum immunologic adjuvant can be used to provide protection against COVID-19. Lack of adjuvants that can induce the required immune responses is a serious impediment to vaccine development against this devastating virus. The approved adjuvants such as aluminum salts and MF59 exhibit a narrow range of activity. In an attempt to solve this problem, it is crucial to develop new adjuvants which can trigger a wide range of immune cells.

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