scholarly journals CD171 multi‑epitope peptide design based on immunoinformatics approach as a cancer vaccine candidate for glioblastoma

2021 ◽  
Author(s):  
Seyed Amir Hossein Mohammadzadeh Hosseini Moghri ◽  
Ghanbar Mahmoodi Chalbatani ◽  
Mojtaba Ranjbar ◽  
Arefeh Abbasian
Keyword(s):  
Tertiary Structure ◽  
Vaccine Development ◽  
T Cell Epitopes ◽  
T Helper 1 ◽  
Epitope Peptide ◽  
Primary Malignancy ◽  
Cholera Toxin Subunit B ◽  
Tlr Agonist ◽  
The Central Nervous System ◽  
Cellular Immune

Abstract Glioblastoma (GB) is a common primary malignancy of the central nervous system, and one of the highly lethal brain tumors. GB cells can promote therapeutic resistance and tumor angiogenesis. The CD171 is an adhesion molecule in neuronal cells that is expressed in glioma cells as a regulator of brain development during the embryonic period. CD171 is one of the immunoglobulin-like CAMs (cell adhesion molecules) families that can be associated with prognosis in a variety of human tumors. The multi-epitope peptide vaccines are based on synthetic peptides with a combination of both B-cell epitopes and T-cell epitopes, which can induce specific humoral or cellular immune responses. Moreover Cholera toxin subunit B (CTB), a novel TLR agonist was utilized in the final construct to polarize CD4+ T cells toward T-helper 1 to induce strong cytotoxic T lymphocytes (CTL) responses. In the present study, several immune-informatics tools were used for analyzing the CD171 sequence and studying the important characteristics of a designed vaccine. The results included the molecular docking, prediction and validation of the secondary and tertiary structure, physicochemical properties, solubility, conservancy, toxicity as well as antigenicity and allergenicity of the promising candidate for a vaccine against CD171. The immuno-informatic analyze suggested 12 predicted multi-epitope peptides, whose construction consists of 582 residues long. Therewith, cloning adaptation of designed vaccine was performed and eventually sequence was inserted into pET30a (+) vector for the application of the anti-glioblastoma vaccine development.

scholarly journals CD171 multi‑epitope peptide design based on immunoinformatics approach as a cancer vaccine candidate for glioblastoma

2021 ◽  
Author(s):  
Seyed Amir Hossein Mohammadzadeh Hosseini Moghri ◽  
Ghanbar Mahmoodi Chalbatani ◽  
Mojtaba Ranjbar ◽  
Arefeh Abbasian
Keyword(s):  
Tertiary Structure ◽  
Vaccine Development ◽  
T Cell Epitopes ◽  
T Helper 1 ◽  
Epitope Peptide ◽  
Primary Malignancy ◽  
Cholera Toxin Subunit B ◽  
Tlr Agonist ◽  
The Central Nervous System ◽  
Cellular Immune

Abstract Glioblastoma (GB) is a common primary malignancy of the central nervous system, and one of the highly lethal brain tumors. GB cells can promote therapeutic resistance and tumor angiogenesis. The CD171 is an adhesion molecule in neuronal cells that is expressed in glioma cells as a regulator of brain development during the embryonic period. CD171 is one of the immunoglobulin-like CAMs (cell adhesion molecules) families that can be associated with prognosis in a variety of human tumors. The multi-epitope peptide vaccines are based on synthetic peptides with a combination of both B-cell epitopes and T-cell epitopes, which can induce specific humoral or cellular immune responses. Moreover Cholera toxin subunit B (CTB), a novel TLR agonist was utilized in the final construct to polarize CD4+ T cells toward T-helper 1 to induce strong cytotoxic T lymphocytes (CTL) responses. In the present study, several immune-informatics tools were used for analyzing the CD171 sequence and studying the important characteristics of a designed vaccine. The results included the molecular docking, prediction and validation of the secondary and tertiary structure, physicochemical properties, solubility, conservancy, toxicity as well as antigenicity and allergenicity of the promising candidate for a vaccine against CD171. The immuno-informatic analyze suggested 12 predicted multi-epitope peptides, whose construction consists of 582 residues long. Therewith, cloning adaptation of designed vaccine was performed and eventually sequence was inserted into pET30a (+) vector for the application of the anti-glioblastoma vaccine development.

scholarly journals CD171 multi‑epitope peptide design based on immunoinformatics approach as a cancer vaccine candidate for glioblastoma

2021 ◽  
Author(s):  
Seyed Amir Hossein Mohammadzadeh Hosseini Moghri ◽  
Arefeh Abbasian
Keyword(s):  
Tertiary Structure ◽  
Vaccine Development ◽  
T Cell Epitopes ◽  
Epitope Peptide ◽  
Primary Malignancy ◽  
Cellular Immune Responses ◽  
The Central Nervous System ◽  
Cellular Immune ◽  
Informatics Tools ◽  
The Brain

Abstract Glioblastoma (GB) is a common primary malignancy of the central nervous system, and one of the highly lethal brain tumors. GB cells can promote therapeutic resistance and tumor angiogenesis. The CD171 is an adhesion molecule in neuronal cells that is expressed in glioma cells; it is a regulator of the brain development. CD171 is one of the immunoglobulin-like CAMs (cell adhesion molecules) families that can be associated with prognosis in a variety of human tumors. The multi-epitope peptide vaccines are based on synthetic peptides with a combination of both B-cell epitopes and T-cell epitopes, which can induce specific humoral or cellular immune responses. In the present study, several immune-informatics tools were used for analyzing the CD171 sequence and studying the important characteristics of a designed vaccine. The results included the prediction and validation of the secondary and tertiary structure, physicochemical properties, solubility, conservancy, toxicity as well as antigenicity and allergenicity of the promising candidate for a vaccine against CD171. The immunoinformatic analysis suggested 12 predicted multi-epitope peptides, whose construction consists of 582 residues long. Therewith, cloning adaptation of designed vaccine was performed and eventually sequence was inserted into pET30a (+) vector for the application of the anti-glioblastoma vaccine development.

scholarly journals Design an efficient multi-epitope peptide vaccine candidate against SARS-CoV-2: An in silico analysis

2020 ◽  
Author(s):  
Zahra Yazdani ◽  
Alireza Rafiei ◽  
Mohammadreza Yazdani ◽  
Reza Valadan
Keyword(s):  
Escherichia Coli ◽  
In Silico ◽  
Tertiary Structure ◽  
Peptide Vaccine ◽  
High Mobility ◽  
In Silico Analysis ◽  
Epitope Peptide ◽  
Cellular And Humoral Immunity ◽  
Cellular Immune ◽  
Immunodominant Epitopes

AbstractBackgroundTo date, no specific vaccine or drug has been proven to be effective for SARS-CoV-2 infection. Therefore, we implemented immunoinformatics approach to design an efficient multi-epitopes vaccine against SARS-CoV-2.ResultsThe designed vaccine construct has several immunodominant epitopes from structural proteins of Spike, Nucleocapsid, Membrane and Envelope. These peptides promote cellular and humoral immunity and Interferon gamma responses. In addition, these epitopes have antigenicity ability and no allergenicity probability. To enhance the vaccine immunogenicity, we used three potent adjuvants; Flagellin, a driven peptide from high mobility group box 1 as HP-91 and human beta defensin 3 protein. The physicochemical and immunological properties of the vaccine structure were evaluated. Tertiary structure of the vaccine protein was predicted and refined by I-Tasser and galaxi refine and validated using Rampage and ERRAT. Results of Ellipro showed 242 residues from vaccine might be conformational B cell epitopes. Docking of vaccine with Toll-Like Receptors 3, 5 and 8 proved an appropriate interaction between the vaccine and receptor proteins. In silico cloning demonstrated that the vaccine can be efficiently expressed in Escherichia coli.ConclusionsThe designed multi epitope vaccine is potentially antigenic in nature and has the ability to induce humoral and cellular immune responses against SARS-CoV-2. This vaccine can interact appropriately with the TLR3, 5, and 8. Also, this vaccine has high quality structure and suitable characteristics such as high stability and potential for expression in Escherichia coli.

scholarly journals Designing a Novel Multi-Epitope Vaccine against SARS-CoV-2; Implication for Viral Binds and Fusion Inhibition through Inducing Neutralizing Antibodies

2021 ◽  
Author(s):  
Seyed Amir Hossein Mohammadzadeh Hosseini Moghri ◽  
Mojtaba Ranjbar ◽  
Hadi Hassannia ◽  
Fatemeh Khakdan
Keyword(s):  
B Cell ◽  
Neutralizing Antibodies ◽  
Vaccine Development ◽  
Vital Role ◽  
Epitope Peptide ◽  
Tertiary Structures ◽  
Angiotensin Converting Enzyme 2 ◽  
Fusion Inhibitors ◽  
Fusion Inhibition ◽  
Cellular Immune

Recently the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has become a pervasive threat to public health so it is an emergency to vaccine development. The SARS-CoV-2 spike (S) glycoprotein plays a vital role in binds and fusion to the angiotensin-converting enzyme 2 (ACE2). The multi-epitope peptide vaccines are capable of inducing the specific humoral or cellular immune responses. In this regard, the RBD and spike cleavage site is the most probable target for vaccine development to inducing binds and fusion inhibitors neutralizing antibodies. In the present study, several immunoinformatics tools are used for analyzing the spike (S) glycoprotein sequence including the prediction of the potential linear B-cell epitopes, B-cell multi-epitope design, secondary and tertiary structures, physicochemical properties, solubility, antigenicity, and allergenicity for the promising vaccine candidate against SARS-CoV-2.

scholarly journals Multi-epitope vaccine design using an immunoinformatics approach for 2019 novel coronavirus (SARS-CoV-2)

2020 ◽  
Author(s):  
Ye Feng ◽  
Min Qiu ◽  
Liang Liu ◽  
Shengmei Zou ◽  
Yun Li ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Peptide Vaccine ◽  
Human Leukocyte ◽  
T Cell Epitopes ◽  
Epitope Peptide ◽  
Leukocyte Antigen ◽  
Cellular Immune Responses ◽  
Rapid Dissemination ◽  
Cellular Immune

AbstractA new coronavirus SARS-CoV-2 has caused over 9.2 million infection cases and 475758 deaths worldwide. Due to the rapid dissemination and the unavailability of specific therapy, there is a desperate need for vaccines to combat the epidemic of SARS-CoV-2. An in silico approach based on the available virus genome was applied to identify 19 high immunogenic B-cell epitopes and 499 human-leukocyte-antigen (HLA) restricted T-cell epitopes. Thirty multi-epitope peptide vaccines were designed by iNeo Suite, and manufactured by solid-phase synthesis. Docking analysis showed stable hydrogen bonds of epitopes with their corresponding HLA alleles. When four vaccine peptide candidates from the spike protein of SARS-CoV-2 were selected to immunize mice, a significantly larger amount of IgG in serum as well as an increase of CD19+ cells in ILNs was observed in peptide-immunized mice compared to the control mice. The ratio of IFN-γ-secreting lymphocytes in CD4+ or CD8+ cells in the peptides-immunized mice were higher than that in the control mice. There were also a larger number of IFN-γ-secreting T cells in spleen in the peptides-immunized mice. This study screened antigenic B-cell and T-cell epitopes in all encoded proteins of SARS-CoV-2, and further designed multi-epitope based peptide vaccine against viral structural proteins. The obtained vaccine peptides successfully elicited specific humoral and cellular immune responses in mice. Primate experiments and clinical trial are urgently required to validate the efficacy and safety of these vaccine peptides.ImportanceSo far, a new coronavirus SARS-CoV-2 has caused over 9.2 million infection cases and 475758 deaths worldwide. Due to the rapid dissemination and the unavailability of specific therapy, there is a desperate need for vaccines to combat the epidemic of SARS-CoV-2. Different from the development approaches for traditional vaccines, the development of our peptide vaccine is faster and simpler. In this study, we performed an in silico approach to identify the antigenic B-cell epitopes and human-leukocyte-antigen (HLA) restricted T-cell epitopes, and designed a panel of multi-epitope peptide vaccines. The resulting SARS-CoV-2 multi-epitope peptide vaccine could elicit specific humoral and cellular immune responses in mice efficiently, displaying its great potential in our fight of COVID-19.

scholarly journals In Silico Identification of Novel B Cell and T Cell Epitopes of Wuhan Coronavirus (2019-nCoV) for Effective Multi Epitope-Based Peptide Vaccine Production

2020 ◽  
Author(s):  
Muhammad Asif Rasheed ◽  
Sohail Raza ◽  
Ali Zohaib ◽  
Tahir Yaqub ◽  
Masood Rabbani ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Vaccine Development ◽  
Peptide Vaccine ◽  
Surface Glycoprotein ◽  
World Health ◽  
Effective Vaccine ◽  
Computer Assisted ◽  
T Cell Epitopes ◽  
Epitope Peptide

During December 2019, a novel coronavirus named as 2019-nCoV, has emerged in Wuhan, China. The human to human transmission of this virus has also been established. Untill now the virus has infected more than seven thousand people and has spread to fifteen countries. The World Health Organization (WHO) has declared 2019-nCoV as global health emergency due to its outburst well beyond China. There is need to develop some vaccines or therapeutics to control or prevent 2019-nCoV infections. The bottleneck with current conventional approaches is that these require longer time for vaccine development. However, computer assisted approaches help us to produce effective vaccine in short time compared with conventional methods. In this study, bioinformatics analysis was used to predict B cell and T cell epitopes of surface glycoprotein of 2019-nCoV that could be suitable to trigger significant immune response. The sequence of surface glycoprotein was collected from the database and analyzed to identify the immunogenic epitope. Both B cell and T cell epitopes were analyzed so the predicted epitopes can stimulate both cellular and humoral immune responses. We predicted 13 B cell and 05 T cell epitopes that later on were joined with GPGPG linker to make a single peptide. This computational approach to design a multi epitope peptide vaccine against emerging 2019-nCoV allows us to find novel immunogenic epitopes against the antigen targets of surface 2019-nCoV surface glycoprotein. This multi epitope peptide vaccine may prove effective to combat 2019-nCoV infections.

Use of T Cell Epitopes for Vaccine Development

2001 ◽  
Vol 1 (3) ◽  
pp. 303-313 ◽  
Author(s):  
H. Sbai ◽  
A. Mehta ◽  
A. DeGroot
Keyword(s):  
T Cell ◽  
Vaccine Development ◽  
T Cell Epitopes

scholarly journals The Anthrax Vaccine Adsorbed Vaccine Generates Protective Antigen (PA)-Specific CD4+ T Cells with a Phenotype Distinct from That of Naïve PA T Cells

2008 ◽  
Vol 76 (10) ◽  
pp. 4538-4545 ◽  
Author(s):  
William W. Kwok ◽  
Junbao Yang ◽  
Eddie James ◽  
John Bui ◽  
Laurie Huston ◽  
...  
Keyword(s):  
T Cells ◽  
Mononuclear Cells ◽  
Protective Antigen ◽  
Ex Vivo ◽  
Cytokine Profile ◽  
T Cell Epitopes ◽  
Peripheral Blood Mononuclear ◽  
Anthrax Vaccine ◽  
Cellular Immune

ABSTRACT Cellular immune responses against protective antigen (PA) of Bacillus anthracis in subjects that received the anthrax vaccine adsorbed (AVA) vaccine were examined. Multiple CD4+ T-cell epitopes within PA were identified by using tetramer-guided epitope mapping. PA-reactive CD4+ T cells with a CD45RA− phenotype were also detected by direct ex vivo staining of peripheral blood mononuclear cells (PBMC) with PA-specific tetramers. Surprisingly, PA-specific T cells were also detected in PBMC of nonvaccinees after a single cycle of in vitro PA stimulation. However, PA-reactive CD4+ T cells in nonvaccinees occurred at lower frequencies than those in vaccinees. The majority of PA-reactive T cells from nonvaccinees were CD45RA+ and exhibited a Th0/Th1 cytokine profile. In contrast, phenotyping and cytokine profile analyses of PA-reactive CD4+ T cells from vaccinees indicated that vaccination leads to commitment of PA-reactive T cells to a Th2 lineage, including generation of PA-specific, pre-Th2 central memory T cells. These results demonstrate that the current AVA vaccine is effective in skewing the development of PA CD4+ T cells to the Th2 lineage. The data also demonstrated the feasibility of using class II tetramers to analyze CD4+ cell responses and lineage development after vaccination.

scholarly journals Protective Vaccine Efficacy of the Complete Form of PPE39 Protein from Mycobacterium tuberculosis Beijing/K Strain in Mice

2017 ◽  
Vol 24 (11) ◽  
Author(s):  
Ahreum Kim ◽  
Yun-Gyoung Hur ◽  
Sunwha Gu ◽  
Sang-Nae Cho
Keyword(s):  
T Cells ◽  
Mycobacterium Tuberculosis ◽  
T Cell ◽  
Vaccine Development ◽  
Protective Efficacy ◽  
Interleukin 2 ◽  
T Cell Epitopes ◽  
Content Type ◽  
Complete Form ◽  
Ifn Γ

ABSTRACT The aim of this study was to evaluate the protective efficacy of MTBK_24820, a complete form of PPE39 protein derived from a predominant Beijing/K strain of Mycobacterium tuberculosis in South Korea. Mice were immunized with MTKB_24820, M. bovis Bacilli Calmette-Guérin (BCG), or adjuvant prior to a high-dosed Beijing/K strain aerosol infection. After 4 and 9 weeks, bacterial loads were determined and histopathologic and immunologic features in the lungs and spleens of the M. tuberculosis-infected mice were analyzed. Putative immunogenic T-cell epitopes were examined using synthetic overlapping peptides. Successful immunization of MTBK_24820 in mice was confirmed by increased IgG responses (P < 0.05) and recalled gamma interferon (IFN-γ), interleukin-2 (IL-2), IL-6, and IL-17 responses (P < 0.05 or P < 0.01) to MTBK_24820. After challenge with the Beijing/K strain, an approximately 0.5 to 1.0 log10 reduction in CFU in lungs and fewer lung inflammation lesions were observed in MTBK_24820-immunized mice compared to those for control mice. Moreover, MTBK_24820 immunization elicited significantly higher numbers of CD4+ T cells producing protective cytokines, such as IFN-γ and IL-17, in lungs and spleens (P < 0.01) and CD4+ multifunctional T cells producing IFN-γ, tumor necrosis factor alpha (TNF-α), and/or IL-17 (P < 0.01) than in control mice, suggesting protection comparable to that of BCG against the hypervirulent Beijing/K strain. The dominant immunogenic T-cell epitopes that induced IFN-γ production were at the N terminus (amino acids 85 to 102 and 217 to 234). Its vaccine potential, along with protective immune responses in vivo, may be informative for vaccine development, particularly in regions where the M. tuberculosis Beijing/K-strain is frequently isolated from TB patients.

scholarly journals Insights into Cross-species Evolution of Novel Human Coronavirus 2019-nCoV and Defining Immune Determinants for Vaccine Development

2020 ◽  
Author(s):  
Arunachalam Ramaiah ◽  
Vaithilingaraja Arumugaswami
Keyword(s):  
Binding Affinity ◽  
Vaccine Development ◽  
Asia Pacific ◽  
Potential Candidate ◽  
T Cell Epitopes ◽  
Live Animal ◽  
Synonymous Mutations ◽  
Wide Range ◽  
Novel Coronavirus ◽  
N Proteins

ABSTRACTNovel Coronavirus (nCoV) outbreak in the city of Wuhan, China during December 2019, has now spread to various countries across the globe triggering a heightened containment effort. This human pathogen is a member of betacoronavirus genus carrying 30 kilobase of single positive-sense RNA genome. Understanding the evolution, zoonotic transmission, and source of this novel virus would help accelerating containment and prevention efforts. The present study reported detailed analysis of 2019-nCoV genome evolution and potential candidate peptides for vaccine development. This nCoV genotype might have been evolved from a bat-CoV by accumulating non-synonymous mutations, indels, and recombination events. Structural proteins Spike (S), and Membrane (M) had extensive mutational changes, whereas Envelope (E) and Nucleocapsid (N) proteins were very conserved suggesting differential selection pressures exerted on 2019-nCoV during evolution. Interestingly, 2019-nCoV Spike protein contains a 39 nucleotide sequence insertion relative to SARS-like bat-SL-CoVZC45/2017. Furthermore, we identified eight high binding affinity (HBA) CD4 T-cell epitopes in the S, E, M and N proteins, which can be commonly recognized by HLA-DR alleles of Asia and Asia-Pacific Region population. These immunodominant epitopes can be incorporated in universal subunit CoV vaccine. Diverse HLA types and variations in the epitope binding affinity may contribute to the wide range of immunopathological outcomes of circulating virus in humans. Our findings emphasize the requirement for continuous surveillance of CoV strains in live animal markets to better understand the viral adaptation to human host and to develop practical solutions to prevent the emergence of novel pathogenic CoV strains.

Sign in / Sign up

Export Citation Format

Share Document