scholarly journals Cellular and humoral immune responses associated with protection in sheep vaccinated against Teladorsagia circumcincta

2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Cynthia Machín ◽  
Yolanda Corripio-Miyar ◽  
Julia N. Hernández ◽  
Tara Pérez-Hernández ◽  
Adam D. Hayward ◽  
...  

AbstractDue to increased anthelmintic resistance, complementary methods to drugs are necessary to control gastrointestinal nematodes (GIN). Vaccines are an environmentally-friendly and promising option. In a previous study, a Teladorsagia circumcincta recombinant sub-unit vaccine was administered to two sheep breeds with different levels of resistance against GIN. In the susceptible Canaria Sheep (CS) breed, vaccinates harboured smaller worms with fewer eggs in utero than the control group. Here, we extend this work, by investigating the cellular and humoral immune responses of these two sheep breeds following vaccination and experimental infection with T. circumcincta. In the vaccinated CS group, negative associations between antigen-specific IgA, IgG2 and Globule Leukocytes (GLs) with several parasitological parameters were established as well as a higher CD4+/CD8+ ratio than in control CS animals, suggesting a key role in the protection induced by the vaccine. In the more resistant Canaria Hair Breed (CHB) sheep the vaccine did not significantly impact on the parasitological parameters studied and none of these humoral associations were observed in vaccinated CHB lambs, although CHB had higher proportions of CD4+ and CD8+ T cells within the abomasal lymph nodes, suggesting higher mucosal T cell activation. Each of the component proteins in the vaccine induced an increase in immunoglobulin levels in vaccinated groups of each breed. However, levels of immunoglobulins to only three of the antigens (Tci-MEP-1, Tci-SAA-1, Tci-ASP-1) were negatively correlated with parasitological parameters in the CS breed and they may be, at least partially, responsible for the protective effect of the vaccine in this breed. These data could be useful for improving the current vaccine prototype.

2012 ◽  
Vol 51 (1) ◽  
pp. 12-13
Author(s):  
Henrike Veninga ◽  
Ellen Borg ◽  
Hakan Kalay ◽  
Yvette van Kooyk ◽  
Georg Kraal ◽  
...  

2018 ◽  
Vol 115 (42) ◽  
pp. 10726-10731 ◽  
Author(s):  
Carlos G. Briseño ◽  
Ansuman T. Satpathy ◽  
Jesse T. Davidson ◽  
Stephen T. Ferris ◽  
Vivek Durai ◽  
...  

CD4+ T follicular helper (TFH) cells support germinal center (GC) reactions promoting humoral immunity. Dendritic cell (DC) diversification into genetically distinct subsets allows for specialization in promoting responses against several types of pathogens. Whether any classical DC (cDC) subset is required for humoral immunity is unknown, however. We tested several genetic models that selectively ablate distinct DC subsets in mice for their impact on splenic GC reactions. We identified a requirement for Notch2-dependent cDC2s, but not Batf3-dependent cDC1s or Klf4-dependent cDC2s, in promoting TFH and GC B cell formation in response to sheep red blood cells and inactivated Listeria monocytogenes. This effect was mediated independent of Il2ra and several Notch2-dependent genes expressed in cDC2s, including Stat4 and Havcr2. Notch2 signaling during cDC2 development also substantially reduced the efficiency of cDC2s for presentation of MHC class II-restricted antigens, limiting the strength of CD4 T cell activation. Together, these results demonstrate a nonredundant role for the Notch2-dependent cDC2 subset in supporting humoral immune responses.


2014 ◽  
Vol 112 (2) ◽  
pp. E156-E165 ◽  
Author(s):  
Roberto A. Maldonado ◽  
Robert A. LaMothe ◽  
Joseph D. Ferrari ◽  
Ai-Hong Zhang ◽  
Robert J. Rossi ◽  
...  

Current treatments to control pathological or unwanted immune responses often use broadly immunosuppressive drugs. New approaches to induce antigen-specific immunological tolerance that control both cellular and humoral immune responses are desirable. Here we describe the use of synthetic, biodegradable nanoparticles carrying either protein or peptide antigens and a tolerogenic immunomodulator, rapamycin, to induce durable and antigen-specific immune tolerance, even in the presence of potent Toll-like receptor agonists. Treatment with tolerogenic nanoparticles results in the inhibition of CD4+ and CD8+ T-cell activation, an increase in regulatory cells, durable B-cell tolerance resistant to multiple immunogenic challenges, and the inhibition of antigen-specific hypersensitivity reactions, relapsing experimental autoimmune encephalomyelitis, and antibody responses against coagulation factor VIII in hemophilia A mice, even in animals previously sensitized to antigen. Only encapsulated rapamycin, not the free form, could induce immunological tolerance. Tolerogenic nanoparticle therapy represents a potential novel approach for the treatment of allergies, autoimmune diseases, and prevention of antidrug antibodies against biologic therapies.


2015 ◽  
Vol 195 (2) ◽  
pp. 519-527 ◽  
Author(s):  
Sarang Tartey ◽  
Kazufumi Matsushita ◽  
Tomoko Imamura ◽  
Atsuko Wakabayashi ◽  
Daisuke Ori ◽  
...  

Blood ◽  
2007 ◽  
Vol 110 (1) ◽  
pp. 193-200 ◽  
Author(s):  
Li-Fan Lu ◽  
Cory L. Ahonen ◽  
Evan F. Lind ◽  
Vanitha S. Raman ◽  
W. James Cook ◽  
...  

The recruitment of tumor necrosis factor receptor–associated factors (TRAFs) 1, 2, 3, 5, and 6 to the CD40 cytoplasmic tail upon CD40 trimerization results in downstream signaling events that ultimately lead to CD40-dependent, thymus-dependent (TD) humoral immune responses. Previously, we have shown signaling through the C-terminal tail of CD40 in the absence of canonical TRAF-binding sites is capable of signaling through an alternative TRAF2-binding site. Here, we demonstrate that B cells from mice harboring CD40 with only the C-terminal tail can activate both canonical and noncanonical NFκB signaling pathways. Moreover, while lacking germinal center formation, several hallmarks of humoral immune responses including clonal B-cell activation/expansion, antibody isotype switching, and affinity maturation remain normal. This study demonstrates a new functional domain in CD40 that controls critical aspects of B-cell immunity in an in vivo setting.


2003 ◽  
Vol 56 (11-12) ◽  
pp. 557-563 ◽  
Author(s):  
Valentina Arsic-Arsenijevic ◽  
Aleksandar Dzamic ◽  
Sanja Mitrovic ◽  
Ivana Radonjic ◽  
Ivana Kranjcic-Zec

Introduction When protozoa enter the blood stream or tissues they can often survive and replicate because they adapt to the resisting natural host defenses. The interaction of immune system with infectious organisms is a dynamic interplay of host mechanisms aimed at eliminating infections and microbial strategies designed to permit survival in the face of powerful effectors mechanisms. Protozoa cause chronic and persistent infections, because natural immunity against them is weak and because protozoa have evolved multiple mechanisms for evading and resisting specific immunity. Natural and specific immune response to protozoa Different protozoa vary greatly in their structural and biochemical properties and stimulate distinct patterns of immune responses and have evolved unique mechanisms for evading specific immunity. Protozoa activate quite distinct specific immune responses, which are different from the responses to fungi, bacteria and viruses. Protozoa may be phagocytozed by macrophages, but many are resistant to phagocytic killing and may even replicate within macrophages. T. brucei gambiense is the best example of protozoa which can induce humoral immune response because of its extra-cellular location. In Leishmania sp. infections, cellular defense mechanisms depend upon CD4+ T-lymphocytes and activate macrophages as effectors cells that are regulated by cytokines of Th1 subset. Plasmodium sp. is a protozoa which show the diversity of defence mechanisms which can be cellular or humoral, depending on Ag and protozoa's location. Immune evasion mechanisms of protozoa Different protozoa have developed remarkably effective ways of resisting specific immunity: a) anatomic sequestration is commonly observed with protozoa Plasmodium and T. gondii; b) some protozoa can become resistant to immune effectors mechanisms: Trypanosoma, Leishmania and T. gondii; c) some protozoa have developed effective mechanisms for varying their surface antigens: Plasmodium and Trypanosoma; d) some protozoa shed their antigen coats, either spontaneously or after binding with specific antibodies: E. histolytica; e) some protozoa alter host immune response by nonspecific and generalized immunosuppression (abnormalities in cytokine production, deficient T cell activation): Trypanosoma, Leishmania, Toxoplasma, Entamoeba. Conclusion Protozoa activate numerous, different immune mechanisms in human body. Evolution, progression and outcome of diseases depend upon these mechanisms. Resent progresses in research have defined and selected Ag as candidates for new vaccines. Better definitions regarding the role of cytokines in protozoaninfections will facilitate rational development of cytokines and cytokine antagonists and their use as immunotherapeutic agents.


2021 ◽  
Author(s):  
Moritz M Hollstein ◽  
Lennart Muensterkoetter ◽  
Michael P Schoen ◽  
Armin Bergmann ◽  
Thea M Husar ◽  
...  

Background: Homologous and heterologous SARS-CoV-2-vaccinations yield different spike protein-directed humoral and cellular immune responses. However, their interdependencies remain elusive. Methods: COV-ADAPT is a prospective, observational cohort study of 417 healthcare workers who received homologous vaccination with Astra (ChAdOx1-S; AstraZeneca) or BNT (BNT162b2; Biontech/Pfizer) or heterologous vaccination with Astra/BNT. We assessed the humoral (anti-spike-RBD-IgG, neutralizing antibodies, antibody avidity) and cellular (spike-induced T cell interferon-y release) immune response in blood samples up to 2 weeks before (T1) and 2 to 12 weeks following secondary immunization (T2). Findings: Initial vaccination with Astra resulted in lower anti-spike-RBD-IgG responses compared to BNT (70+/-114 vs. 226+/-279 BAU/ml, p<0.01) at T1, whereas T cell activation did not differ significantly. Booster vaccination with BNT proved superior to Astra at T2 (anti-spike-RBD-IgG: Astra/BNT 2387+/-1627 and BNT/BNT 3202+/-2184 vs. Astra/Astra 413+/-461 BAU/ml, both p<0.001; spike-induced T cell interferon-y; release: Astra/BNT 5069+/-6733 and BNT/BNT 4880+/-7570 vs. Astra/Astra 1152+/-2243 mIU/ml, both p<0.001). No significant differences were detected between BNT-boostered groups at T2. For Astra, we observed no booster effect on T cell activation. We found associations between anti-spike-RBD-IgG levels (Astra/BNT and BNT/BNT) and T cell responses (Astra/Astra and Astra/BNT) from T1 to T2. There were also links between levels of anti-spike-RBD-IgG and T cell at both time points (all groups combined). All regimes yielded neutralizing antibodies and increased antibody avidity at T2. Interpretation: Interdependencies between humoral and cellular immune responses differ between common SARS-CoV-2 vaccination regimes. T cell activation is unlikely to compensate for poor humoral responses. Funding: Deutsche Forschungsgemeinschaft (DFG), ER723/3-1


2021 ◽  
Author(s):  
Melika Haghighi ◽  
Akbar khorasani ◽  
Pegah Karimi ◽  
Rouhollah Keshavarz ◽  
Mehdi Mahdavi

Abstract Several inactivated SARS-CoV-2 vaccines were approved for human use but are not highly potent. Here, different formulations of inactivated SARS-CoV-2 virus in Alum, Montanide 51VG and Montanide ISA720VG adjuvants were developed and then immune responses were assessed. SARS-CoV-2 virus was inactivated with formalin and formulated in the adjuvants. BALB/c mice were immunized subcutaneously with 4µg of experimental vaccines on days 0 and 14 and two weeks after the final immunization, IL-4 and IFN-γ cytokines, CTL activity and specific IgG titer and IgG1, IgG2a, IgG2a/IgG1 ratio and also anti-RBD IgG response were assessed. Immunization with SARS-CoV-2-Montanide ISA51VG showed a significant increase in IFN-γ cytokine versus SARS-CoV-2-Alum, SARS-CoV-2-Montanide ISA720VG and control groups (P<0.0033). Cytokine IL-4 response in SARS-CoV-2-Alum group showed a significant increase versus SARS-CoV-2-Montanide ISA51VG, SARS-CoV-2-Montanide ISA720VG and control groups (P<0.0206). In addition, SARS-CoV-2-Montanide ISA51VG vaccine induced the highest IFN-γ/IL-4 cytokine ratio versus other groups (P<0.0004). CTL activity in SARS-CoV-2- Montanide ISA51 VG and SARS-CoV-2-Montanide ISA720 VG groups showed a significant increase versus SARS-CoV-2-Alum and control groups (P<0.0075). Specific IgG titer in SARS-CoV-2- Montanide ISA51 VG and SARS-CoV-2-Montanide ISA720VG showed significant increase versus SARS-CoV-2-Alum and control groups (P<0.0143). Results of specific IgG1and IgG2a level in SARS-COV-2-Alum, SARS-COV-2-Montanide ISA51VG and SARS-COV-2-Montanide ISA720VG vaccine showed a significant increase versus the control group (P<0.0001) but SARS-COV-2-Montanide ISA51VG and SARS-COV-2-Montanide ISA 720VG groups showed highest IgG2a/IgG1 ratio and a significant increase versus SARS-COV-2-Alum group (P<0.0379). Results of anti-RBD IgG response showed that inactivated SARS-COV-2+Alum and SARS-COV-2-Montanide ISA 720VG vaccine groups demonstrated a significant increase versus SARS-COV-2-Montanide ISA51VG group. It seems that the type of vaccine formulation is a critical parameter that effect on immunologic patterns and vaccine potency. Here, results showed that human compatible oil-based adjuvants were more potent than Alum adjuvant in the induction of cellular and humoral immune responses versus SARS-CoV-2 virus.


2020 ◽  
Vol 72 (3) ◽  
pp. 915-920
Author(s):  
Khalid Naveed ◽  
Aqeel Javeed ◽  
Muhammad Ashraf ◽  
Amjad Riaz ◽  
Aamir Ghafoor ◽  
...  

ABSTRACT Nabumetone is used to reduce the pain and inflammation in rheumatoid arthritis. In the current study, immunomodulatory effect of Nabumetone is investigated in mice. The control group was administered normal saline orally as placebo. Nabumetone was administered orally via gavage in two treatment groups at 14mg/kg.b.w. doses and 28mg/kgb.w., respectively. Haemagglutination (HA) assay, Jerne hemolytic plaque and mice lethality assays were applied. In HA assay, the titer was significantly decreased in Nabumetone treatment groups (P< 0.001). In Jerne hemolytic plaque formation assay, there was a significant reduction (P< 0.001) in number of plaques in Nabumetone treated groups when compared with control. In mice lethality assay, there was a significant difference in mortality ratio of mice in control and Nabumetone treated groups (P< 0.001). Therefore, it is concluded that Nabumetone suppresses the humoral immune response in mice.


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