The Experts below are selected from a list of 24774 Experts worldwide ranked by ideXlab platform
Manojit Bhattacharya - One of the best experts on this subject based on the ideXlab platform.
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development of epitope based Peptide Vaccine against novel coronavirus 2019 sars cov 2 immunoinformatics approach
Journal of Medical Virology, 2020Co-Authors: Manojit Bhattacharya, Ashish Ranjan Sharma, Prasanta Patra, Pratik Ghosh, Garima Sharma, Bidhan Chandra Patra, Chiranjib ChakrabortyAbstract:Recently, a novel coronavirus (SARS-COV-2) emerged which is responsible for the recent outbreak in Wuhan, China. Genetically, it is closely related to SARS-CoV and MERS-CoV. The situation is getting worse and worse, therefore, there is an urgent need for designing a suitable Peptide Vaccine component against the SARS-COV-2. Here, we characterized spike glycoprotein to obtain immunogenic epitopes. Next, we chose 13 Major Histocompatibility Complex-(MHC) I and 3 MHC-II epitopes, having antigenic properties. These epitopes are usually linked to specific linkers to build Vaccine components and molecularly dock on toll-like receptor-5 to get binding affinity. Therefore, to provide a fast immunogenic profile of these epitopes, we performed immunoinformatics analysis so that the rapid development of the Vaccine might bring this disastrous situation to the end earlier.
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Identification and Design of a Next-Generation Multi Epitopes Bases Peptide Vaccine Candidate Against Prostate Cancer: An In Silico Approach
Cell Biochemistry and Biophysics, 2020Co-Authors: Prasanta Patra, Manojit Bhattacharya, Ashish Ranjan Sharma, Pratik Ghosh, Garima Sharma, Bidhan Chandra Patra, Bidyut Mallick, Chiranjib ChakrabortyAbstract:Prostate cancer (PCa) is the second most diagnosed cancer in men and ranked fifth in overall cancer diagnosis. During the past decades, it has arisen as a significant life-threatening disease in men at an older age. At the early onset of illness when it is in localized form, radiation and surgical treatments are applied against this disease. In case of adverse situations androgen deprivation therapy, chemotherapy, hormonal therapy, etc. are widely used as a therapeutic element. However, studies found the occurrences of several side effects after applying these therapies. In current work, several immunoinformatic techniques were applied to formulate a multi-epitopic Vaccine from the overexpressed antigenic proteins of PCa. A total of 13 epitopes were identified from the five prostatic antigenic proteins (PSA, PSMA, PSCA, STEAP, and PAP), after validation with several in silico tools. These epitopes were fused to form a Vaccine element by (GGGGS)_3 Peptide linker. Afterward, 5, 6-dimethylxanthenone-4-acetic acid (DMXAA) was used as an adjuvant to initiate and induce STING-mediated cytotoxic cascade. In addition, molecular docking was performed between the Vaccine element and HLA class I antigen with the low ACE value of −251 kcal/mol which showed a significant binding. Molecular simulation using normal mode analysis (NMA) illustrated the docking complex as a stable one. Therefore, this observation strongly indicated that our multi epitopes bases Peptide Vaccine molecule will be an effective candidate for the treatment of the PCa.
Hirotsugu Uemura - One of the best experts on this subject based on the ideXlab platform.
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a phase 2 randomized controlled trial of personalized Peptide Vaccine immunotherapy with low dose dexamethasone versus dexamethasone alone in chemotherapy naive castration resistant prostate cancer
European Urology, 2016Co-Authors: Kazuhiro Yoshimura, Akira Yamada, Takafumi Minami, Masahiro Nozawa, Takahiro Kimura, Shin Egawa, Hiroyuki Fujimoto, Kyogo Itoh, Hirotsugu UemuraAbstract:Abstract Background It is well known that the prognosis of castration-resistant prostate cancer (CRPC) is poor, and several immunotherapeutic strategies have been applied to the clinical trials. Research on immunotherapy has been of special interest for the treatment of CRPC for years. Objective To evaluate the safety of personalized Peptide Vaccine (PPV) immunotherapy and its clinical outcomes. Design, setting, and participants A phase 2 randomized controlled trial of PPV immunotherapy with low-dose dexamethasone versus dexamethasone alone for chemotherapy-naive CRPC began in 2008. Eligible patients (prostate-specific antigen [PSA] Outcome measurements and statistical analysis PSA, progression-free survival (PFS), time to initiation of chemotherapy, and overall survival (OS) were analyzed using the Kaplan-Meier method, a log-rank test, and proportional hazard analysis. Results and limitations Overall, 37 patients received Peptide vaccinations and 35 received dexamethasone alone. The primary end point was PSA PFS, which was significantly longer in the vaccination group than in the dexamethasone group (22.0 vs 7.0 mo; p =0.0076). Median OS was also significantly longer in the vaccination group (73.9 vs 34.9 mo; p =0.00084). The relatively small number of patients enrolled is the major limitation of the study. Conclusions PPV immunotherapy was well tolerated and associated with longer PSA PFS and OS in men with chemotherapy-naive CRPC. A larger phase 3 study is needed to confirm our findings. Patient summary We compared clinical outcomes of the treatment with personalized Peptide Vaccine plus dexamethasone versus dexamethasone alone. Our data provide promising evidence of clinical benefit for Peptide Vaccines. Trial registration UMIN-CTR: 000000959.
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a phase 2 randomized controlled trial of personalized Peptide Vaccine immunotherapy with low dose dexamethasone versus dexamethasone alone in chemotherapy naive castration resistant prostate cancer
European Urology, 2016Co-Authors: Kazuhiro Yoshimura, Akira Yamada, Takafumi Minami, Masahiro Nozawa, Takahiro Kimura, Shin Egawa, Hiroyuki Fujimoto, Kyogo Itoh, Hirotsugu UemuraAbstract:Abstract Background It is well known that the prognosis of castration-resistant prostate cancer (CRPC) is poor, and several immunotherapeutic strategies have been applied to the clinical trials. Research on immunotherapy has been of special interest for the treatment of CRPC for years. Objective To evaluate the safety of personalized Peptide Vaccine (PPV) immunotherapy and its clinical outcomes. Design, setting, and participants A phase 2 randomized controlled trial of PPV immunotherapy with low-dose dexamethasone versus dexamethasone alone for chemotherapy-naive CRPC began in 2008. Eligible patients (prostate-specific antigen [PSA] Outcome measurements and statistical analysis PSA, progression-free survival (PFS), time to initiation of chemotherapy, and overall survival (OS) were analyzed using the Kaplan-Meier method, a log-rank test, and proportional hazard analysis. Results and limitations Overall, 37 patients received Peptide vaccinations and 35 received dexamethasone alone. The primary end point was PSA PFS, which was significantly longer in the vaccination group than in the dexamethasone group (22.0 vs 7.0 mo; p =0.0076). Median OS was also significantly longer in the vaccination group (73.9 vs 34.9 mo; p =0.00084). The relatively small number of patients enrolled is the major limitation of the study. Conclusions PPV immunotherapy was well tolerated and associated with longer PSA PFS and OS in men with chemotherapy-naive CRPC. A larger phase 3 study is needed to confirm our findings. Patient summary We compared clinical outcomes of the treatment with personalized Peptide Vaccine plus dexamethasone versus dexamethasone alone. Our data provide promising evidence of clinical benefit for Peptide Vaccines. Trial registration UMIN-CTR: 000000959.
Chiranjib Chakraborty - One of the best experts on this subject based on the ideXlab platform.
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development of epitope based Peptide Vaccine against novel coronavirus 2019 sars cov 2 immunoinformatics approach
Journal of Medical Virology, 2020Co-Authors: Manojit Bhattacharya, Ashish Ranjan Sharma, Prasanta Patra, Pratik Ghosh, Garima Sharma, Bidhan Chandra Patra, Chiranjib ChakrabortyAbstract:Recently, a novel coronavirus (SARS-COV-2) emerged which is responsible for the recent outbreak in Wuhan, China. Genetically, it is closely related to SARS-CoV and MERS-CoV. The situation is getting worse and worse, therefore, there is an urgent need for designing a suitable Peptide Vaccine component against the SARS-COV-2. Here, we characterized spike glycoprotein to obtain immunogenic epitopes. Next, we chose 13 Major Histocompatibility Complex-(MHC) I and 3 MHC-II epitopes, having antigenic properties. These epitopes are usually linked to specific linkers to build Vaccine components and molecularly dock on toll-like receptor-5 to get binding affinity. Therefore, to provide a fast immunogenic profile of these epitopes, we performed immunoinformatics analysis so that the rapid development of the Vaccine might bring this disastrous situation to the end earlier.
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Identification and Design of a Next-Generation Multi Epitopes Bases Peptide Vaccine Candidate Against Prostate Cancer: An In Silico Approach
Cell Biochemistry and Biophysics, 2020Co-Authors: Prasanta Patra, Manojit Bhattacharya, Ashish Ranjan Sharma, Pratik Ghosh, Garima Sharma, Bidhan Chandra Patra, Bidyut Mallick, Chiranjib ChakrabortyAbstract:Prostate cancer (PCa) is the second most diagnosed cancer in men and ranked fifth in overall cancer diagnosis. During the past decades, it has arisen as a significant life-threatening disease in men at an older age. At the early onset of illness when it is in localized form, radiation and surgical treatments are applied against this disease. In case of adverse situations androgen deprivation therapy, chemotherapy, hormonal therapy, etc. are widely used as a therapeutic element. However, studies found the occurrences of several side effects after applying these therapies. In current work, several immunoinformatic techniques were applied to formulate a multi-epitopic Vaccine from the overexpressed antigenic proteins of PCa. A total of 13 epitopes were identified from the five prostatic antigenic proteins (PSA, PSMA, PSCA, STEAP, and PAP), after validation with several in silico tools. These epitopes were fused to form a Vaccine element by (GGGGS)_3 Peptide linker. Afterward, 5, 6-dimethylxanthenone-4-acetic acid (DMXAA) was used as an adjuvant to initiate and induce STING-mediated cytotoxic cascade. In addition, molecular docking was performed between the Vaccine element and HLA class I antigen with the low ACE value of −251 kcal/mol which showed a significant binding. Molecular simulation using normal mode analysis (NMA) illustrated the docking complex as a stable one. Therefore, this observation strongly indicated that our multi epitopes bases Peptide Vaccine molecule will be an effective candidate for the treatment of the PCa.
S K Gakhar - One of the best experts on this subject based on the ideXlab platform.
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3cl hydrolase based multiepitope Peptide Vaccine against sars cov 2 using immunoinformatics
Journal of Medical Virology, 2020Co-Authors: Renu Jakhar, Samander Kaushik, S K GakharAbstract:The present study provides the first multiepitope Vaccine construct using the 3CL hydrolase protein of SARS-CoV-2. The coronavirus 3CL hydrolase (Mpro) enzyme is essential for proteolytic maturation of the virus. This study was based on immunoinformatics and structural vaccinology strategies. The design of the multiepitope Vaccine was built using helper T-cell and cytotoxic T-cell epitopes from the 3CL hydrolase protein along with an adjuvant to enhance immune response; these are joined to each other by short Peptide linkers. The Vaccine also carries potential B-cell linear epitope regions, B-cell discontinuous epitopes, and interferon-I³-inducing epitopes. Epitopes of the constructed multiepitope Vaccine were found to be antigenic, nonallergic, nontoxic, and covering large human populations worldwide. The Vaccine construct was modeled, validated, and refined by different programs to achieve a high-quality three-dimensional structure. The resulting high-quality model was applied for conformational B-cell epitope selection and docking analyses with toll-like receptor-3 for understanding the capability of the Vaccine to elicit an immune response. In silico cloning and codon adaptation were also performed with the pET-19b plasmid vector. The designed multiepitope Peptide Vaccine may prompt the development of a Vaccine to control SARS-CoV-2 infection.
Eli Estey - One of the best experts on this subject based on the ideXlab platform.
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pr1 Peptide Vaccine induces specific immunity with clinical responses in myeloid malignancies
Leukemia, 2017Co-Authors: Muzaffar H. Qazilbash, Peter F. Thall, R. Rios, S. Kanodia, Kathryn Ruisaard, Sergio Giralt, Eli Estey, Eric D Wieder, X Wang, Jorge E CortesAbstract:PR1, an HLA-A2-restricted Peptide derived from both proteinase 3 and neutrophil elastase, is recognized on myeloid leukemia cells by cytotoxic T lymphocytes (CTLs) that preferentially kill leukemia and contribute to cytogenetic remission. To evaluate safety, immunogenicity and clinical activity of PR1 vaccination, a phase I/II trial was conducted. Sixty-six HLA-A2+ patients with acute myeloid leukemia (AML: 42), chronic myeloid leukemia (CML: 13) or myelodysplastic syndrome (MDS: 11) received three to six PR1 Peptide vaccinations, administered subcutaneously every 3 weeks at dose levels of 0.25, 0.5 or 1.0 mg. Patients were randomized to the three dose levels after establishing the safety of the highest dose level. Primary end points were safety and immune response, assessed by doubling of PR1/HLA-A2 tetramer-specific CTL, and the secondary end point was clinical response. Immune responses were noted in 35 of 66 (53%) patients. Of the 53 evaluable patients with active disease, 12 (24%) had objective clinical responses (complete: 8; partial: 1 and hematological improvement: 3). PR1-specific immune response was seen in 9 of 25 clinical responders versus 3 of 28 clinical non-responders (P=0.03). In conclusion, PR1 Peptide Vaccine induces specific immunity that correlates with clinical responses, including molecular remission, in AML, CML and MDS patients.
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PR1 Peptide Vaccine induces specific immunity with clinical responses in myeloid malignancies
Leukemia, 2016Co-Authors: Muzaffar H. Qazilbash, Eric Wieder, Peter F. Thall, Xin Shelley Wang, R. Rios, Sijie Lu, S. Kanodia, Kathryn Ruisaard, Sergio Giralt, Eli EsteyAbstract:PR1 Peptide Vaccine induces specific immunity with clinical responses in myeloid malignancies