scholarly journals A T-Cell Epitope-Based Multi-Epitope Vaccine Designed Using Human HLA Specific T Cell Epitopes Induces a Near-Sterile Immunity against Experimental Visceral Leishmaniasis in Hamsters

Vaccines ◽  
2021 ◽  
Vol 9 (10) ◽  
pp. 1058
Author(s):  
Aryandra Arya ◽  
Sunil K. Arora
Keyword(s):  
T Cell ◽  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Cell Epitope ◽  
Effective Vaccine ◽  
T Cell Epitope ◽  
Hamster Model ◽  
Vaccine Candidates

Visceral leishmaniasis is a neglected tropical disease affecting 12 million people annually. Even in the second decade of the 21st century, it has remained without an effective vaccine for human use. In the current study, we designed three multiepitope vaccine candidates by the selection of multiple IFN-γ inducing MHC-I and MHC-II binder T-cell specific epitopes from three previously identified antigen genes of Leishmania donovani from our lab by an immuno-informatic approach using IFNepitope, the Immune Epitope Database (IEDB) T cell epitope identification tools, NET-MHC-1, and NET MHC-2 webservers. We tested the protective potential of these three multiepitope proteins as a vaccine in a hamster model of visceral leishmaniasis. The immunization data revealed that the vaccine candidates induced a very high level of Th1 biased protective immune response in-vivo in a hamster model of experimental visceral leishmaniasis, with one of the candidates inducing a near-sterile immunity. The vaccinated animals displayed highly activated monocyte macrophages with the capability of clearing intracellular parasites due to increased respiratory burst. Additionally, these proteins induced activation of polyfunctional T cells secreting INF-γ, TNF-α, and IL-2 in an ex-vivo stimulation of human peripheral blood mononuclear cells, further supporting the protective nature of the designed candidates.

scholarly journals A T-Cell Epitope-Based Multi-Epitope Vaccine Designed Using Human HLA Specific T Cell Epitopes Induces Sterile Immunity against Experimental Visceral Leishmaniasis in Hamsters

2021 ◽  
Author(s):  
Aryandra Arya ◽  
Sunil K Arora
Keyword(s):  
T Cell ◽  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Human Peripheral Blood ◽  
Cell Epitope ◽  
Effective Vaccine ◽  
Hamster Model ◽  
Vaccine Candidates

Visceral Leishmaniasis is a neglected tropical disease affecting 12 million people annually. Even in the second decade of the 21st century, it has remained without an effective vaccine for human use. In the current study, we have designed three multiepitope vaccine candidates by the selection of multiple IFN-γ inducing MHC-I and MHC-II binder T-cell specific epitopes from 3 previously identified antigen genes of Leishmania donovani from our lab, by immune-informatic approach using IFNepiotpe, NET-MHC-1 and NET MHC-2 webservers. We have tested the protective potential of these three multiepitope proteins as vaccine in a hamster model of visceral leishmaniasis. The immunization data revealed that the vaccine candidates induced a very high level of Th-1 biased protective immune response in-vivo in a hamster model of experimental visceral Leishmaniasis, with one of the candidates inducing a sterile immunity. The vaccinated animals displayed highly activated monocyte macrophages with the capability of clearing intracellular parasites due to increased respiratory burst. Additionally, these proteins induced activation of polyfunctional T cells secreting INF-γ, TNF-α, and IL-2 in ex-vivo stimulation of human peripheral blood mononuclear cells, further supporting the protective nature of designed candidates.

scholarly journals Characterization of Plasmodium falciparum Proteome at Asexual Blood Stages for Screening of Effective Vaccine Candidates: An Immunoinformatics Approach

2015 ◽  
Vol 7 ◽  
pp. III.S24755 ◽  
Author(s):  
Satarudra Prakash Singh ◽  
Vishal Verma ◽  
Bhartendu Nath Mishra
Keyword(s):  
Plasmodium Falciparum ◽  
T Cell ◽  
Cell Epitope ◽  
Epitope Prediction ◽  
Proteome Analysis ◽  
Effective Vaccine ◽  
Secretory Proteins ◽  
Vaccine Candidates ◽  
Proteome Level

Malaria is a complex parasitic disease that is currently causing great concerns globally owing to the resistance to antimalarial drugs and lack of an effective vaccine. The present study involves the characterization of extracellular secretory proteins as vaccine candidates derived from proteome analysis of Plasmodium falciparum at asexual blood stages of malaria. Among the screened 32 proteins, 31 were predicted as antigens by the VaxiJen program, and 26 proteins had less than two transmembrane spanning regions predicted using the THMMM program. Moreover, 10 and 5 proteins were predicted to contain secretory signals by SignalP and TargetP, respectively. T-cell epitope prediction using MULTIPRED2 and NetCTL programs revealed that most of the predicted antigens are immunogenic and contain more than 10% supertype and 5% promiscuous epitopes of HLA-A, -B, or -DR. We anticipate that T-cell immune responses against asexual blood stages of Plasmodium are dispersed on a relatively large number of parasite antigens. This is the first report, to the best of our knowledge, offering new insights, at the proteome level, for the putative screening of effective vaccine candidates against the malaria pathogen. The findings also suggest new ways forward for the modern omics-guided vaccine target discovery using reverse vaccinology.

scholarly journals IL-10 and TGF-β Induced Arginase Expression Contributes to Deficient Nitric Oxide Response in Human Visceral Leishmaniasis

2021 ◽  
Vol 10 ◽  
Author(s):  
Manu Kupani ◽  
Smriti Sharma ◽  
Rajeev Kumar Pandey ◽  
Rajiv Kumar ◽  
Shyam Sundar ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Visceral Leishmaniasis ◽  
Leishmania Donovani ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
No Production ◽  
Peripheral Blood Mononuclear ◽  
Before And After ◽  
Plasma Nitrite

Nitric oxide (NO) is an anti-microbial effector of the innate immune system which plays major role in non-specific killing of various pathogens including protozoan parasites. However, due to subversion of the host’s immune processes by pathogens, suboptimal production of NO is frequently found in many infection models. Previous studies have shown suppressed NO production during Leishmania donovani infection, the causative agent of visceral leishmaniasis (VL). Availability of L-Arginine, a semi-essential amino acid is required for inducible nitric oxide synthase (iNOS) mediated NO production. However, arginase is another enzyme, which if expressed concomitantly, may strongly compete for L-Arginine, and suppress NO production by iNOS. In the present study, plasma nitrite and arginase levels were measured in VL patients before and after successful drug treatment, endemic and non-endemic healthy donors. We observed significantly lower NO levels in the plasma of VL patients as compared to endemic controls, which improved significantly post-treatment. Significantly elevated arginase activity was also observed in the plasma of VL patients, which may be associated with NO deficiency. VL patients also showed significantly higher levels of IL-10 and TGF-β, which are known to regulate expression of arginase in various immune cells. In vitro studies with human peripheral blood mononuclear cells (PBMCs) further corroborated the role of IL-10 and TGF-β in arginase mediated suppression of NO production.

Design, creation and in vitro testing of a reduced immunogenicity humanized anti-CD25 monoclonal antibody that retains functional activity

2019 ◽  
Vol 32 (12) ◽  
pp. 543-554
Author(s):  
Marcia Stickler ◽  
Anita Reddy ◽  
Joanna M Xiong ◽  
Melanie H Wong ◽  
Yoshiko Akamatsu ◽  
...  
Keyword(s):  
T Cell ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Cell Epitope ◽  
Cd4 T Cell ◽  
Peripheral Blood Mononuclear ◽  
Epitope Region ◽  
Human Sequence ◽  
Amino Acid Mutations

Abstract Humanized and fully human sequence-derived therapeutic antibodies retain the capacity to induce anti-drug antibodies. Daclizumab (humanized version of the murine anti-Tac antibody; E.HAT) was selected for a proof of concept application of engineering approaches to reduce potential immunogenicity due to its demonstrated immunogenicity in the clinic. Reduced immunogenicity variants of E.HAT were created by identifying and modifying a CD4+ T cell epitope region in the VH region. Variant epitope region peptides were selected for their reduced capacity to induce CD4+ T cell proliferative responses in vitro. Variant antibody molecules were created, and CD25 affinity and potency were similar to the unmodified parent antibody. Fab fragments from the variant antibodies induced a lower frequency and magnitude of responses in human peripheral blood mononuclear cells proliferation tests. By the empirical selection of two amino acid mutations, fully functional humanized E.HAT antibodies with reduced potential to induce immune responses in vitro were created.

scholarly journals Identification of a T-Cell Epitope That Is Globally Conserved among Outer Membrane Proteins (OMPs) OMP7, OMP8, and OMP9 of Anaplasma marginale Strains and with OMP7 from the A. marginale subsp. centrale Vaccine Strain

2016 ◽  
Vol 24 (1) ◽  
Author(s):  
James R. Deringer ◽  
Elkin G. Forero-Becerra ◽  
Massaro W. Ueti ◽  
Joshua E. Turse ◽  
James E. Futse ◽  
...  
Keyword(s):  
T Cell ◽  
Outer Membrane ◽  
Vaccine Strain ◽  
Outer Membrane Proteins ◽  
Cell Epitope ◽  
Anaplasma Marginale ◽  
Immune Serum ◽  
T Cell Epitope ◽  
Content Type ◽  
Vaccine Candidates

ABSTRACT Within the protective outer membrane (OM) fraction of Anaplasma marginale, several vaccine candidates have emerged, including a family of OM proteins (OMPs) 7 to 9, which share sequence identity with each other and with the single protein OMP7 in the vaccine strain A. marginale subsp. centrale. A. marginale OMPs 7 to 9 are logical vaccine candidates because they are surface exposed, present in the OM immunogen and protective cross-linked OM proteins, recognized by immune serum IgG2 and T cells in cattle immunized with OM, and recognized by immune serum IgG2 from cattle immunized with the A. centrale vaccine strain. We report the identification of a globally conserved 9-amino-acid T-cell epitope FLLVDDAI/VV shared between A. centrale vaccine strain OMP7 and the related A. marginale OMPs 7 to 9, where position 8 of the peptide can be isoleucine or valine. The epitope is conserved in American A. marginale strains, in the Australia Gypsy Plains strain, and in multiple field isolates from Ghana. This epitope, together with additional T-cell epitopes that are present within these proteins, should be considered for inclusion in a multivalent vaccine for A. marginale that can provide protection against disease caused by globally distributed bacterial strains.

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