In Silico Design of a Novel Multi-Epitope Peptide Vaccine Against Hepatocellular Carcinoma

2020 ◽  
Vol 17 (9) ◽  
pp. 1164-1176
Author(s):  
Fatemeh Motamedi Dehbarez ◽  
Navid Nezafat ◽  
Shirin Mahmoodi
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Lymphocytes ◽  
Immune Responses ◽  
Tandem Repeats ◽  
3D Structure ◽  
Peptide Vaccine ◽  
Humoral Immune ◽  
Innovative Therapy

Background: Hepatocellular Carcinoma (HCC) is a prevalent cancer in the world. As yet, there is no medication for complete treatment of HCC. Objective: There is a critical need to search for an innovative therapy for HCC. Recently, multiepitope vaccines have been introduced as effective immunotherapy approach against HCC. Methods: In this research, several immunoinformatics methods were applied to create an original multi-epitope vaccine against HCC consisting of CD8+ cytolytic T lymphocytes (CTLs) epitopes selected from α- fetoprotein (AFP), glypican-3 (GPC3), aspartyl-β-hydroxylase (ASPH); CD4+ helper T lymphocytes (HTLs) epitopes from tetanus toxin fragment C (TTFC), and finally, two tandem repeats of HSP70407-426 were used which stimulated strong innate and adaptive immune responses. All the mentioned parts were connected together by relevant linkers. Results: According to physicochemical, structural, and immunological results, the designed vaccine is stable, non-allergen, antigen; it also has a high-quality 3D structure, and numerous linear and conformational B cell epitopes, whereby this vaccine may stimulate efficient humoral immunity. Conclusion: Center on the collected results, the designed vaccine potentially can induce cellular and humoral immune responses in HCC cases; nonetheless, the efficiency of vaccine must be approved within in vitro and in vivo immunological analyzes.

Chondroitin sulfate activates B cells in vitro, expands CD138+cells in vivo, and interferes with established humoral immune responses

2014 ◽  
Vol 96 (1) ◽  
pp. 65-72 ◽  
Author(s):  
Hilke Brühl ◽  
Josef Cihak ◽  
Nicole Goebel ◽  
Yvonne Talke ◽  
Kerstin Renner ◽  
...  
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
Chondroitin Sulfate ◽  
Humoral Immune ◽  
Humoral Immune Responses

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 Deglycosylation of the 45/47-Kilodalton Antigen Complex of Mycobacterium tuberculosis Decreases Its Capacity To Elicit In Vivo or In Vitro Cellular Immune Responses

1999 ◽  
Vol 67 (11) ◽  
pp. 5567-5572 ◽  
Author(s):  
Félix Romain ◽  
Cynthia Horn ◽  
Pascale Pescher ◽  
Abdelkader Namane ◽  
Michel Riviere ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
T Lymphocytes ◽  
Immune Responses ◽  
Delayed Type Hypersensitivity ◽  
Cellular Immune Responses ◽  
Antigen Complex ◽  
Cellular Immune ◽  
Living Bacteria

ABSTRACT A protection against a challenge with Mycobacterium tuberculosis is induced by previous immunization with living attenuated mycobacteria, usually bacillus Calmette-Guérin (BCG). The 45/47-kDa antigen complex (Apa) present in culture filtrates of BCG of M. tuberculosis has been identified and isolated based on its ability to interact mainly with T lymphocytes and/or antibodies induced by immunization with living bacteria. The protein is glycosylated. A large batch of Apa was purified from M. tuberculosis culture filtrate to determine the extent of glycosylation and its role on the expression of the immune responses. Mass spectrometry revealed a spectrum of glycosylated molecules, with the majority of species bearing six, seven, or eight mannose residues (22, 24, and 17%, respectively), while others three, four, or five mannoses (5, 9, and 14%, respectively). Molecules with one, two, or nine mannoses were rare (1.5, 3, and 3%, respectively), as were unglycosylated species (in the range of 1%). To eliminate the mannose residues linked to the protein, the glycosylated Apa molecules were chemically or enzymatically treated. The deglycosylated antigen was 10-fold less active than native molecules in eliciting delayed-type hypersensitivity reactions in guinea pigs immunized with BCG. It was 30-fold less active than native molecules when assayed in vitro for its capacity to stimulate T lymphocytes primed in vivo. The presence of the mannose residues on the Apa protein was essential for the antigenicity of the molecules in T-cell-dependent immune responses in vitro and in vivo.

Immunological and pathological responses in BALB/c mice induced by genetic administration ofTc13 Tul antigen ofTrypanosoma cruzi

Parasitology ◽  
2006 ◽  
Vol 132 (6) ◽  
pp. 855-866 ◽  
Author(s):  
G. A. GARCÍA ◽  
M. R. ARNAIZ ◽  
S. A. LAUCELLA ◽  
M. I. ESTEVA ◽  
N. AINCIART ◽  
...  
Keyword(s):  
Immune Responses ◽  
Dna Encoding ◽  
Genetic Immunization ◽  
Humoral Immune ◽  
Specific Memory ◽  
Family Protein ◽  
Ifn Γ

Tc13 is atrans-sialidase family protein ofTrypanosoma cruzi, the aetiological agent of Chagas' disease. Recently,in vitrostudies had suggested thatTc13 might participate in the pathogenesis of the disease. In order to study the role ofTc13 antigens in anin vivomodel, we administered plasmid DNA encoding aTc13 antigen from the Tulahuén strain (Tc13 Tul) to BALB/c mice and evaluated the immunological and pathological manifestations as well as the capacity of this antigen to confer protection againstT. cruziinfection.Tc13 Tul immunization did not elicit a detectable humoral immune response but induced specific memory T-cells with no capacity to produce IFN-γ. Five months after DNA-immunization withTc13 Tul, signs of hepatotoxicity and reactive changes in the heart, liver and spleen were observed in 40–80% of mice. WhenTc13 Tul DNA-immunized animals were challenged with trypomastigotes, a significant decrease in parasitaemia in early and late acute phase was observed without modification in the survival rate. Surprisingly,Tc13 Tul-immunized mice chronically infected withT. cruzishowed a decrease in the severity of heart damage. We conclude that, in BALB/c mice, genetic immunization withTc13 Tul mainly induces immune responses associated with pathology.

scholarly journals The Adjuvant Activity ofEpimediumPolysaccharide-Propolis Flavone Liposome on Enhancing Immune Responses to Inactivated Porcine Circovirus Vaccine in Mice

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Yunpeng Fan ◽  
Liwei Guo ◽  
Weifeng Hou ◽  
Chao Guo ◽  
Weimin Zhang ◽  
...  
Keyword(s):  
Immune Responses ◽  
Mrna Expression ◽  
Porcine Circovirus Type ◽  
Porcine Circovirus ◽  
Adjuvant Activity ◽  
Humoral Immune ◽  
Pcv2 Vaccine ◽  
Better Than

Objectives.The adjuvant activity ofEpimediumpolysaccharide-propolis flavone liposome (EPL) was investigated in vitro and in vivo.Methods.In vitro, the effects of EPL at different concentrations on splenic lymphocytes proliferation and mRNA expression of IFN-γand IL-6 were determined. In vivo, the adjuvant activities of EPL, EP, and mineral oil were compared in BALB/c mice through vaccination with inactivated porcine circovirus type 2 (PCV2) vaccine.Results.In vitro, EPL promoted lymphocytes proliferation and increased the mRNA expression of IFN-γand IL-6, and the effect was significantly better than EP at all concentrations. In vivo, EPL significantly promoted the lymphocytes proliferation and the secretion of cytokines and improved the killing activity of NK cells, PCV2-specific antibody titers, and the proportion of T-cell subgroups. The effects of EPL were significantly better than EP and oil adjuvant at most time points.Conclusion.EPL could significantly improve both PCV2-specific cellular and humoral immune responses, and its medium dose had the best efficacy. Therefore, EPL would be exploited in an effective immune adjuvant for inactivated PCV2 vaccine.

scholarly journals Immunological Function in Mice Lacking the Rac-Related GTPase RhoG

2004 ◽  
Vol 24 (2) ◽  
pp. 719-729 ◽  
Author(s):  
Elena Vigorito ◽  
Sarah Bell ◽  
Barbara J. Hebeis ◽  
Helen Reynolds ◽  
Simon McAdam ◽  
...  
Keyword(s):  
Immune Responses ◽  
T Cell Proliferation ◽  
Cross Linking ◽  
Low Molecular Weight ◽  
Targeted Disruption ◽  
Mild Phenotype ◽  
Humoral Immune ◽  
B And T Lymphocytes

ABSTRACT RhoG is a low-molecular-weight GTPase highly expressed in lymphocytes that activates gene transcription and promotes cytoskeletal reorganization in vitro. To study the in vivo function of RhoG, we generated mice homozygous for a targeted disruption of the RhoG gene. Despite the absence of RhoG, the development of B and T lymphocytes was unaffected. However, there was an increase in the level of serum immunoglobulin G1 (IgG1) and IgG2b as well as a mild increase of the humoral immune response to thymus-dependent antigens. In addition, B- and T-cell proliferation in response to antigen receptor cross-linking was slightly increased. Although RhoG deficiency produces a mild phenotype, our experiments suggest that RhoG may contribute to the negative regulation of immune responses. The lack of a strong phenotype could indicate a functional redundancy of RhoG with other Rac proteins in lymphocytes.

Delivery of mRNA into Dendritic Cells Using Novel Transfer Peptides Leads to Prolonged Antigen Expression and Potent Immune Responses In Vivo.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4884-4884
Author(s):  
Karrune Woan ◽  
Axel Heiser ◽  
Philipp Dahm ◽  
Johannes Vieweg ◽  
Zhen Su
Keyword(s):  
Dendritic Cells ◽  
Immune Responses ◽  
Rna Binding ◽  
Antigen Expression ◽  
Human Monocyte ◽  
Humoral Immune ◽  
Humoral Immune Responses ◽  
Effective Delivery

Abstract We have previously shown that vaccination with RNA-transfected DC is a potent strategy to stimulate CTL and antitumor immunity in cancer patients. In this study, we investigated whether novel transfer peptides derived from the RNA-binding region of the HIV-1 nucleocapsid protein could be utilized for effective delivery of mRNA into human monocyte-derived dendritic cells (DC). Here we show that both peptide-mediated mRNA delivery and electroporation of DC with mRNA resulted in efficient gene transfer. However, the use of transfer peptides led to prolonged antigen expression and did not negatively affect the viability of DC, the migratory capacity of matured DC, and the production of cytokines by these cells in vitro. In murine studies, DC loaded with transfer peptide-mRNA complexes were clearly superior, compared to mRNA-electroporated DC, in stimulating antigen-specific CTL, CD4+ T cell, and antibody responses. Importantly, no transfer peptide-specific cellular or humoral immune responses were detected in vaccinated mice. Our data suggest that vaccination with transfer peptide-mRNA-loaded DC may represent a promising strategy to stimulate potent anti-tumor immune responses in a vaccination setting.

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