scholarly journals In silico and in vitro Evaluation of Mimetic Peptides as Potential Antigen Candidates for Prophylaxis of Leishmaniosis

2021 ◽  
Vol 8 ◽  
Author(s):  
Deborah Carbonera Guedes ◽  
Manuel Hospinal Santiani ◽  
Joyce Carvalho ◽  
Carlos Ricardo Soccol ◽  
João Carlos Minozzo ◽  
...  
Keyword(s):  
Parasite Infection ◽  
Spot Synthesis ◽  
Inflammatory Reactions ◽  
Humoral Immune ◽  
Immune Balance ◽  
Immunogenic Peptides ◽  
Almost All ◽  
Cellular Immune ◽  
Th1 And Th2

Antigen formulation is the main feature for the success of leishmaniosis diagnosis and vaccination, since the disease is caused by different parasite species that display particularities which determine their pathogenicity and virulence. It is desirable that the antigens are recognized by different antibodies and are immunogenic for almost all Leishmania species. To overcome this problem, we selected six potentially immunogenic peptides derived from Leishmania histones and parasite membrane molecules obtained by phage display or spot synthesis and entrapped in liposome structures. We used these peptides to immunize New Zealand rabbits and determine the immunogenic capacity of the chimeric antigen. The peptides induced the production of antibodies as a humoral immune response against L. braziliensis or L. infantum. Next, to evaluate the innate response to induce cellular activation, macrophages from the peptide mix-immunized rabbits were infected in vitro with L. braziliensis or L. infantum. The peptide mix generated the IFN-γ, IL-12, IL-4 and TGF-β that led to Th1 and Th2 cellular immune responses. Interestingly, this mix of peptides also induced high expression of iNOS. These results suggest that the mix of peptides derived from histone and parasites membrane molecules was able to mimic parasites proteins and induce cytokines important to CD4+ T cell Th1 and Th2 differentiation and effector molecule to control the parasite infection. Finally, this peptide induced an immune balance that is important to prevent immunopathological disorders, inflammatory reactions, and control the parasite infection.

scholarly journals Prostaglandin E2 receptor 3 signaling is induced in placentas with unexplained recurrent pregnancy losses

2018 ◽  
Vol 7 (5) ◽  
pp. 749-761 ◽  
Author(s):  
Yao Ye ◽  
Aurelia Vattai ◽  
Nina Ditsch ◽  
Christina Kuhn ◽  
Martina Rahmeh ◽  
...  
Keyword(s):  
Hormone Secretion ◽  
First Trimester ◽  
Control Group ◽  
Prostaglandin E ◽  
Inflammatory Reactions ◽  
Inflammatory Microenvironment ◽  
Immune Balance ◽  
Beta Hcg ◽  
Recurrent Pregnancy Losses

Although an inflammatory microenvironment is required for successful implantation, an inflammatory overreaction is one of the causes of unexplained recurrent pregnancy losses (uRPL). Prostaglandin E2 (PGE2) plays a pivotal role in regulating immune balance during early pregnancy, and it can stimulate inflammatory reactions via prostaglandin E2 receptor 3 (EP3). However, the role of PGE2 receptor signaling in the uRPL remains unknown. We aimed to investigate whether EP3 signaling is involved in the mechanism of uRPL. Via immunohistochemistry we could show that the expression of cyclooxygenase-2, EP3 and G protein alpha inhibitor 1 (Gi1) was enhanced in the decidua of the uRPL group in comparison to the control group in first-trimester placentas. In vitro, we demonstrated that sulprostone (an EP1/EP3 agonist) inhibited the secretion of beta-hCG and progesterone in JEG-3 cells and the secretion of beta-hCG in HTR-8/SVneo cells while it induced the expression of plasminogen activator inhibitor type 1 in JEG-3 cells. In addition, PGE2/sulprostone was able to stimulate the expression of Gi1, phosphorylated-extracellular signal-regulated kinases 1/2 (p-ERK1/2) and p53. L-798,106 (an EP3-specific antagonist) suppressed the expression of EP3 and p-ERK1/2 without affecting the secretion of beta-hCG. Elevated activation of EP3 signaling in first-trimester placentas plays an important role in regulating the inflammatory microenvironment, the hormone secretion of extravillous trophoblasts and the remodeling of extracellular matrix in the fetal-maternal interface. L-798,106 might be a ‘potential therapeutic candidate’ for the treatment of uRPL.

scholarly journals Nonviable Burkholderia mallei Induces a Mixed Th1- and Th2-Like Cytokine Response in BALB/c Mice

2002 ◽  
Vol 70 (5) ◽  
pp. 2319-2325 ◽  
Author(s):  
Kei Amemiya ◽  
Gary V. Bush ◽  
David DeShazer ◽  
David M. Waag
Keyword(s):  
Interleukin 2 ◽  
Cytokine Response ◽  
Burkholderia Mallei ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Homologous Antigen ◽  
Immunoglobulin Subclasses ◽  
Nonviable Cell ◽  
Cellular Immune ◽  
Th1 And Th2

ABSTRACT Nonviable cell preparations of Burkholderia mallei, the causative agent of glanders, were evaluated as potential vaccine candidates in a BALB/c murine model. Three different B. mallei cell preparations plus Alhydrogel were evaluated: a heat-killed preparation, an irradiation-inactivated preparation, and a preparation of a capsule-negative mutant strain which had been irradiation inactivated. BALB/c mice were vaccinated twice with the different B. mallei preparations, and spleens and sera were collected to determine their cellular and humoral immune responses. All three bacterial cell preparations had essentially the same results in two cellular immune response assays. In a splenocyte proliferation assay, the amount of cell proliferation in response to the homologous immunogen, concanavalin A, or lipopolysaccharide was similar for all the cell preparations. Also, splenocytes from the inoculated mice expressed interleukin 2 (IL-2), gamma interferon, and small amounts of IL-4 and IL-5, and more IL-10 cytokine in the presence of the homologous antigen. When the immunoglobulin subclasses from these mice were examined, they all produced higher levels of IgG1 than IgG2a subclasses. The higher ratio of IgG1 to IgG2a was not due to the amount of the immunogen or the adjuvant (Alhydrogel) used in the BALB/c mice. The cell preparations did not protect the vaccinated mice from a live challenge (>300 50% lethal doses). Our results suggest that in BALB/c mice, a mixed T-helper-cell-like response to nonviable B. mallei is obtained, as demonstrated by a Th1- and Th2-like cytokine response and a Th2-like subclass immunoglobulin response. This may be the reason for the inability of the B. mallei cells that were examined as candidate vaccines to protect the mice from a live challenge.

scholarly journals Augmentation of in vitro humoral immune responses in the mouse by an antibody to IgD.

1980 ◽  
Vol 152 (3) ◽  
pp. 493-506 ◽  
Author(s):  
F D Finkelham ◽  
V L Woods ◽  
S B Wilburn ◽  
J J Mond ◽  
K E Stein ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Total Serum ◽  
Adjuvant Effect ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Almost All ◽  
T Cell Help

Heterologous anti-delta-chain antibodies have an adjuvant effect on specific in vivo humoral immune responses to simultaneously, or subsequently, injected antigens in the rat and rhesus monkey. We have used a hybridoma-secreted antibody that binds murine delta-chain of the allotype (4.22aM delta a) to study this phenomenon in the mouse and to investigate the mechanism of this effect. Injection of 4.22aM delta a into BALB/c mice removes almost all surface IgD (sIgD) from splenic B lymphocites. sIgD does not reappear until the serum level of 4.22aM delta a decreased 5-7 d after injection. 4.22aM delta a fails to induce detectable proliferation or to raise total serum Ig levels substantially above control values. However, 4.22aM dalta a injected 24 h before antigen elicits an approximately twofold enhancement of serum IgM and a 3- to 10-fold enhancement of serum IgG anti-trintriphenyl (TNP) antibodies in response to immunization with optimal doses of TNP-Ficoll or TNP-sheep red blood cells (TNP-SRBC). 4.22aM delta a injected 1 wk before or 3 d after TNP-SRBC, however, has no effect on IgG anti-TNP levels. The adjuvant effect of anti-delta-chain antibody was markedly decreased when suboptimal antigen doses were used. Furthermore, even in the case of TNP-Ficoll, a relatively T-independent antigen, the ability of 4.22aM dalta a to enhance the anti-TNP antibody response was T cell dependent. Our data suggest that the binding of anti-delta-chain antibody to cell sIgD may partially activate B lymphocytes and make them more capable of differentiating into antibody-secreting cells when stimulated by antigen-specific T cell help.

scholarly journals Epitope Mapping of the Diphtheria Toxin and Development of an ELISA-Specific Diagnostic Assay

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 313
Author(s):  
Salvatore Giovanni De-Simone ◽  
Larissa Rodrigues Gomes ◽  
Paloma Napoleão-Pêgo ◽  
Guilherme Curty Lechuga ◽  
Jorge Soares de Pina ◽  
...  
Keyword(s):  
B Cell ◽  
Diphtheria Toxin ◽  
High Performance ◽  
Catalytic Domain ◽  
Elisa Test ◽  
Antigenic Determinants ◽  
Enzyme Linked Immunosorbent Assay ◽  
Spot Synthesis ◽  
Humoral Immune

Background: The diphtheria toxoid antigen is a major component in pediatric and booster combination vaccines and is known to raise a protective humoral immune response upon vaccination. Although antibodies are considered critical for diphtheria protection, little is known about the antigenic determinants that maintain humoral immunity. Methods: One-hundred and twelve 15 mer peptides covering the entire sequence of diphtheria toxin (DTx) protein were prepared by SPOT synthesis. The immunoreactivity of membrane-bound peptides with sera from mice immunized with a triple DTP vaccine allowed mapping of continuous B-cell epitopes, topological studies, multiantigen peptide (MAP) synthesis, and Enzyme-Linked Immunosorbent Assay (ELISA) development. Results: Twenty epitopes were identified, with two being in the signal peptide, five in the catalytic domain (CD), seven in the HBFT domain, and five in the receptor-binding domain (RBD). Two 17 mer (CB/Tx-2/12 and CB/DTx-4–13) derived biepitope peptides linked by a Gly-Gly spacer were chemically synthesized. The peptides were used as antigens to coat ELISA plates and assayed with human (huVS) and mice vaccinated sera (miVS) for in vitro diagnosis of diphtheria. The assay proved to be highly sensitive (99.96%) and specific (100%) for huVS and miVS and, when compared with a commercial ELISA test, demonstrated a high performance. Conclusions: Our work displayed the complete picture of the linear B cell IgG response epitope of the DTx responsible for the protective effect and demonstrated sufficient specificity and eligibility for phase IIB studies of some epitopes to develop new and fast diagnostic assays.

scholarly journals Recurrent acute hepatitis following the use of factor VIII concentrates

Blood ◽  
1980 ◽  
Vol 55 (5) ◽  
pp. 748-751
Author(s):  
TJ Myers ◽  
CL Tembrevilla-Zubiri ◽  
AU Klatsky ◽  
FR Rickles
Keyword(s):  
Immune Response ◽  
Factor Viii ◽  
Acute Hepatitis ◽  
Antigenic Protein ◽  
Humoral Immune ◽  
Recurrent Hepatitis ◽  
Factor Viii Concentrates ◽  
Cellular Immune ◽  
Unusual Type

During a 3-yr period, a patient with hemophilia A experienced 5 episodes of acute hepatitis within 7–16 days following 5 separate infusions of factor VIII (FVIII) concentrates. Although the exact mechanism of the recurrent hepatitis remains unclear, these episodes most likely represented repeated allergic reactions to an antigenic protein derived from the FVIII concentrates. Although no evidence was found for a specific humoral immune response to FVIII in the circulation of the patient, an isolated cellular immune response was suggested by the finding of in vitro lymphocyte stimulation in response to the FVIII concentrate. This unusual type of posttransfusion hepatitis must be added to the list of adverse responses to FVIII concentrates.

scholarly journals Minimizing the risk of allo-sensitization to optimize the benefit of allogeneic cardiac-derived stem/progenitor cells

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Hocine R. Hocine ◽  
Hicham El Costa ◽  
Noemie Dam ◽  
Jerome Giustiniani ◽  
Itziar Palacios ◽  
...  
Keyword(s):  
Immune Response ◽  
Progenitor Cells ◽  
Solid Phase ◽  
Clinical Investigation ◽  
Hla Antibodies ◽  
Paracrine Effects ◽  
Binding Strength ◽  
Humoral Immune ◽  
Cellular Immune

Abstract Allogeneic human cardiac-derived stem/progenitor cells (hCPC) are currently under clinical investigation for cardiac repair. While cellular immune response against allogeneic hCPC could be part of their beneficial-paracrine effects, their humoral immune response remains largely unexplored. Donor-specific HLA antibodies (DSA-HLA-I/DSA-HLA-II), primary elements of antibody-mediated allograft injury, might present an unidentified risk to allogeneic hCPC therapy. Here we established that the binding strength of anti-HLA monoclonal antibodies delineates hCPC proneness to antibody-mediated injury. In vitro modeling of clinical setting demonstrated that specific DSA-HLA-I of high/intermediate binding strength are harmful for hCPC whereas DSA-HLA-II are benign. Furthermore, the Luminex-based solid-phase assays are suitable to predict the DSA-HLA risk to therapeutic hCPC. Our data indicate that screening patient sera for the presence of HLA antibodies is important to provide an immune-educated choice of allogeneic therapeutic cells, minimize the risk of precipitous elimination and promote the allogeneic reparative effects.

scholarly journals Epitope Mapping of the Diphtheria Toxin and Development of an ELISA-Specific Diagnostic Assay

2021 ◽  
Author(s):  
Salvatore Giovanni De-Simone ◽  
Larissa Rodrigues Gomes ◽  
Paloma Napoleão-Pêgo ◽  
Guilherme Curty Lechuga ◽  
Jorge Soares de Pina ◽  
...  
Keyword(s):  
B Cell ◽  
High Performance ◽  
Elisa Test ◽  
Antigenic Determinants ◽  
Spot Synthesis ◽  
Diagnostic Assays ◽  
Humoral Immune ◽  
Entire Sequence ◽  
Membrane Bound

(1) Background: The diphtheria toxoid antigen is a major component in pediatric and booster combination vaccines and is known to raise a protective humoral immune response upon vaccination. Although antibodies are considered critical for diphtheria protection, little is known about the antigenic determinants that maintain humoral immunity. (2) Methods: One hundred twelve 15-mer peptides covering the entire sequence of DTx protein were prepared by Spot-synthesis. Membrane-bound peptides immunoreactivity with sera from mice immunized with triple DTP vaccine allowed mapping of continuous B-cell epitopes, topological studies, MAPs synthesis, and ELISA development. (3) Results: Twenty epitopes were identified, being 2 in the signal peptide, 5 in the CD, 7 in the HBFT domain, and 5 in the RBD. Two 17-mer (CB/Tx-2/12 and CB/DTx-4-13) derived bi-epitope peptides linked by a Gly-Gly spacer were chemically synthesized. The peptides were used as antigens to coat ELISA plates and assayed with human (huVS) and mice vaccined sera (miVS) for in vitro diagnosis of diphtheria. The assay proved to be highly sensitive (99.96%) and specific (100%) either for huVS and miVS and when compared with a commercial ELISA test, demonstrate high performance. (4) Conclusions: Our work displayed the complete picture of the linear B cell IgG response epitope of the DTx responsible for the protective effect and demonstrated the specificity and eligibility to enter phase IIB studies of some epitopes to develop new and fast diagnostic assays.

scholarly journals Recurrent acute hepatitis following the use of factor VIII concentrates

Blood ◽  
1980 ◽  
Vol 55 (5) ◽  
pp. 748-751 ◽  
Author(s):  
TJ Myers ◽  
CL Tembrevilla-Zubiri ◽  
AU Klatsky ◽  
FR Rickles
Keyword(s):  
Immune Response ◽  
Factor Viii ◽  
Acute Hepatitis ◽  
Antigenic Protein ◽  
Humoral Immune ◽  
Recurrent Hepatitis ◽  
Factor Viii Concentrates ◽  
Cellular Immune ◽  
Unusual Type

Abstract During a 3-yr period, a patient with hemophilia A experienced 5 episodes of acute hepatitis within 7–16 days following 5 separate infusions of factor VIII (FVIII) concentrates. Although the exact mechanism of the recurrent hepatitis remains unclear, these episodes most likely represented repeated allergic reactions to an antigenic protein derived from the FVIII concentrates. Although no evidence was found for a specific humoral immune response to FVIII in the circulation of the patient, an isolated cellular immune response was suggested by the finding of in vitro lymphocyte stimulation in response to the FVIII concentrate. This unusual type of posttransfusion hepatitis must be added to the list of adverse responses to FVIII concentrates.

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