Tansiri, Yada

Preferred name

Tansiri, Yada

Main Affiliation

Faculty of Medicine

yada.ta@kmitl.ac.th

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Leptospira borgpetersenii Leucine-Rich Repeat Proteins Provide Strong Protective Efficacy as Novel Leptospiral Vaccine Candidates
(2023-01-01)
Prapong, Siriwan
;
Tansiri, Yada
;
Sritrakul, Tepyuda
;
Sripattanakul, Sineenat
;
Sopitthummakhun, Aukkrimapann
Leucine-rich repeat (LRR) proteins are advocated for being assessed in vaccine development. Leptospiral LRR proteins were identified recently in silico from the genome of Leptospira borgpetersenii serogroup Sejroe, the seroprevalence of leptospiral infections of cattle in Thailand. Two LRR recombinant proteins, rKU_Sej_LRR_2012M (2012) and rhKU_Sej_LRR_2271 (2271), containing predicted immunogenic epitopes, were investigated for their cross-protective efficacies in an acute leptospirosis model with heterologous Leptospira serovar Pomona, though, strains from serogroup Sejroe are host-adapted to bovine, leading to chronic disease. Since serovar Pomona is frequently reported as seropositive in cattle, buffaloes, pigs, and dogs in Thailand and causes acute and severe leptospirosis in cattle by incidental infection, the serogroup Sejroe LRR proteins were evaluated for their cross-protective immunity. The protective efficacies were 37.5%, 50.0%, and 75.0% based on the survival rate for the control, 2012, and 2271 groups, respectively. Sera from 2012-immunized hamsters showed weak bactericidal action compared to sera from 2271-immunized hamsters (p < 0.05). Therefore, bacterial tissue clearances, inflammatory responses, and humoral and cell-mediated immune (HMI and CMI) responses were evaluated only in 2271-immunized hamsters challenged with virulent L. interrogans serovar Pomona. The 2271 protein induced prompt humoral immune responses (p < 0.05) and leptospiral tissue clearance, reducing tissue inflammation in immunized hamsters. In addition, protein 2271 and its immunogenic peptides stimulated splenocyte lymphoproliferation and stimulated both HMI and CMI responses by activating Th1 and Th2 cytokine gene expression in vaccinated hamsters. Our data suggest that the immunogenic potential renders rhKU_Sej_LRR_2271 protein a promising candidate for the development of a novel cross-protective vaccine against animal leptospirosis.
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New potent epitopes from Leptospira borgpetersenii for the stimulation of humoral and cell-mediated immune responses: Experimental and theoretical studies
(2021-01-01)
Tansiri, Yada
;
Sritrakul, Tepyuda
;
Saparpakorn, Patchreenart
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Boondamnern, Timporn
;
Chimprasit, Aunlika
The rhKU_Sej_LRR_2271 protein is introduced as one of the leptospiral vaccine candidates since it contains the predicted immunogenic epitopes. The in-silico sequence and structural based analysis have been used in this study to analyze MHC class I and class II-restricted epitopes of the protein. Six epitope prediction programs were employed, which the epitopes with high prediction scores from each program were aligned. The 21 of potentially unrestrained epitopes with prediction scores above the cut-off value from at least two prediction programs were selected. The 3D-molecular modeling, docking, and molecular dynamic simulation were performed to evaluate the affinity binding between peptide-MHC complex and T-cell receptor. One promising epitope, which is 171-LLFLPLIKI, showed the potency in binding to both MHC class I and II alleles. Two newly designed peptides containing epitopes which can bind to over 3 of MHC alleles, LL17:171-LLFLPLIKILYVDRNKL-187 and SL19:209-SLNSGIKALPFNYEKLVNL-227, significantly increased interferon-gamma (IFNg)-producing specific T-cell responses in the rhKU_Sej_LRR_2271 immunized rabbits compared to nonimmunized rabbits. The LL17 peptide can also induce interferon-gamma-producing specific CD4+ T-cell responses in the immunized rabbits. For the evaluation of humoral immune responses, the immunized rabbits have a significantly greater amount of specific IgG in plasma than the nonimmunized rabbits. Ex-vivo study of T-cell responses in animal model using flow cytometry confirmed an accomplishment of the theoretically in-silico analysis for discovering potential T-cell epitopes of the protein. The results show that the rhKU_Sej_LRR_2271 protein containing promiscuous T-cell epitopes, which can induce both humoral and cell-mediated immune responses, is a prospective protein candidate for leptospiral vaccine development.
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Dimorphism in the T-cell receptor constant region affects T-cell function, phenotype and HIV outcome
(2019-07-15)
Kaewpreedee, Prathanporn
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Boonrat, Potchara
;
Tansiri, Yada
;
Rowland-Jones, Sarah L.
;
Hansasuta, Pokrath
Objectives:CD8+ T cells recognize human leukocyte antigen-peptide complex through the T-cell receptor. Although amino acid variation in T-cell receptor variable chains often affects antigen specificity, dimorphism in the beta chain constant region (TRBC1 and TRBC2) is not thought to affect T-cell function. A recent study suggested that adoptive transfer of TRBC1-specific chimeric antigen-receptor-T cells provided an option for T-cell leukemia therapy that preserved T-cell immunity in the TRBC2 subset. This raises an important question as to whether TRBC1+T cells are qualitatively different from TRBC2+T cells.Design:Cross-sectional study.Methods:Sixty-six antiretroviral therapy-naive HIV-infected individuals, including 19 viraemic controllers and 47 noncontrollers, were enrolled. Peripheral blood mononuclear cells were isolated for T-cell functional assays, tetramer analyses, TRBC1 staining and immunophenotyping.Results:Viraemic controllers had a higher proportion of circulating TRBC1+T cells than noncontrollers, raising the possibility that TRBC1+T cells might be associated with HIV control. TRBC1+T cells also showed more functional T-cell responses against both HIV and cytomegalovirus (P < 0.01). The immunophenotypes of TRBC1-bearing T cells were skewed towards naive and central memory phenotypes, whereas the majority of TRBC2-expressing T cells were terminally differentiated. Inverse correlations were observed between %TRBC1+T cells and HIV plasma viral load, which was most pronounced for CD8+ T cells (r =-0.7096, P = 0.00002357).Conclusion:These data suggest that TRBC1+T-cell responses are of better quality than their TRBC2 counterparts, which should be considered in immunotherapeutic strategies for HIV infection. Conversely, depletion of TRBC1+T cells as part of the treatment of TRBC1+ T-cell malignancies may lead to compromised T-cell response quality.

Tansiri, Yada

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