scholarly journals Immunogenicity of Multiple Antigenic Peptides (MAP) Based on B and T cell Epitopes of E2 Glycoprotein of Chikungunya Virus in Murine System

2017 ◽  
Vol 4 (2) ◽  
Author(s):  
Nagar PK ◽  
Manmohan P ◽  
Kolli VK ◽  
Rao DN
Keyword(s):  
T Cell ◽  
Chikungunya Virus ◽  
Antigenic Peptides ◽  
T Cell Epitopes ◽  
Multiple Antigenic Peptides ◽  
E2 Glycoprotein

scholarly journals In Silico Identification of Chikungunya Virus B- and T-Cell Epitopes with High Antigenic Potential for Vaccine Development

Viruses ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2360
Author(s):  
Gilma G. Sánchez-Burgos ◽  
Nallely M. Montalvo-Marin ◽  
Edgar R. Díaz-Rosado ◽  
Ernesto Pérez-Rueda
Keyword(s):  
T Cell ◽  
Chikungunya Virus ◽  
Vaccine Development ◽  
Human Proteome ◽  
Antigenic Peptides ◽  
T Cell Epitopes ◽  
B Cell Epitopes ◽  
Vaccine Candidates ◽  
In Silico Identification ◽  
Best Parameters

Reverse vaccinology is an outstanding strategy to identify antigens with high potential for vaccine development. Different parameters of five prediction programs were used to assess their sensitivity and specificity to identify B-cell epitopes of Chikungunya virus (CHIKV) strains reported in the IEDB database. The results, based on the use of 15 to 20 mer epitopes and the polyproteins to which they belong, were compared to establish the best parameters to optimize the prediction of antigenic peptides of the Mexican strain CHIKV AJV21562.1. LBtope showed the highest specificity when we used the reported epitopes and polyproteins but the worst sensitivity with polyproteins; ABCpred had similar specificity to LBtope only with the epitopes reported and showed moderate specificity when we used polyproteins for the predictions. Because LBtope was more reliable in predicting true epitopes, it was used as a reference program to predict and select six novel epitopes of the Mexican strain of CHIKV according to prediction frequency, viral genome localization, and non-homology with the human proteome. On the other hand, six bioinformatics programs were used with default parameters to predict T-cell epitopes in the CHIKV strains AJV21562.1 and AJV21561.1. The sequences of the polyproteins were analyzed to predict epitopes present in the more frequent HLA alleles of the Mexican population: DQA1*03011, DQA1*0401, DQA1*0501, DQB1*0201, DQB1*0301, DQB1*0302, and DQB1*0402. Fifteen predicted epitopes in the non-structural and 15 predicted epitopes in the structural polyprotein (9- to 16-mers) with the highest scores of each allele were compared to select epitopes with at least 80% identity. Next, the epitopes predicted with at least two programs were aligned to the human proteome, and 12 sequences without identity with the human proteome were identified as potential antigenic candidates. This strategy would be useful to evaluate vaccine candidates against other viral diseases affecting the countries of the Americas and to increase knowledge about these diseases.

scholarly journals 793 Targeting engineered interleukin-2 (IL-2) to antigen specific T cells via novel biologic platforms

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A828-A828
Author(s):  
Raymond Moniz ◽  
Ahmet Vakkasoglu ◽  
Zohra Merazga ◽  
Tina Daigneault ◽  
Steve Quayle ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Tumor Cells ◽  
Immune Cells ◽  
Interleukin 2 ◽  
Binding Pocket ◽  
Tumor Escape ◽  
Antigenic Peptides ◽  
T Cell Epitopes ◽  
Cell Repertoire

BackgroundA key challenge with IL-2 immunotherapy for cancers is lack of selectivity for anti-tumor immune cells and safety liabilities related to indiscriminate activation of immune cells. The CUE-100 series of Immuno-STATs (ISTs) are designed to selectively activate tumor-specific T cells while avoiding IL-2 toxicities due to systemic activation. CUE-100 series ISTs are rationally engineered Fc fusion proteins comprised of bivalent tumor-peptide-HLA (pHLA) complexes and four affinity-attenuated IL-2 molecules to preferentially engage and activate tumor-specific T cells directly in the patient. Emerging clinical data from our lead candidate CUE-101, which targets HPV-specific T cells in 2L+ R/M HNSCCC, provides PoC for the approach and builds confidence for broad applications in numerous cancers. Building on the CUE-100 series framework, our Neo-STAT (NST) platform contains HLA molecules manufactured with an “empty” peptide-binding pocket, into which diverse tumor-peptides can be chemically conjugated, hence addressing tumor heterogeneity in a cost- and time-efficient manner. Our RDI-STAT (Re-Directed Immuno-STAT) platform further expands the CUE-100 series by redirecting the pre-existing protective viral-specific T cell repertoire to target tumor cells via scFv moieties. RDI-STATs are designed to circumvent potential tumor escape mechanisms linked to HLA loss or defects in antigen-presenting pathways. We present here preclinical data supporting the mechanism of action of these platforms to enhance anti-tumor immune responses.MethodsNSTs were engineered with “empty” HLA-A*0201, into which relevant antigenic peptides were conjugated, and assessed for capacity to expand T cells. RDI-STATs were engineered with TAA-specific scFv and viral-specific pHLA complexes, and assessed for their capacity to induce redirected killing of tumor cells while avoiding systemic activation of all T cells.ResultsThe NST platform demonstrated that different T cell epitopes can be efficiently conjugated into the HLA-binding pocket, and that these molecules activate and expand antigen specific T cells in vitro. RDI-STATs were able to expand anti-viral T cell repertoires and drive anti-viral T cell redirected killing of TAA-expressing cells. In contrast to pan anti-CD3 bispecific molecules, RDI-STATs demonstrated significantly lower induction of pro-inflammatory cytokines.ConclusionsThe IST, NST, and RDI-STAT platforms provide novel opportunities for selective targeting of IL-2 to tumor-relevant T cells while avoiding global immune activation and cytokine release. The scalability and versatility of NSTs highlight the potential to target multiple TAA T cell responses, while RDI-STATs highlight a novel means to harness antiviral immunity against cancer, especially in cases where the tumor may escape immune detection due to loss of HLA.

scholarly journals Uncovering the Tumor Antigen Landscape: What to Know about the Discovery Process

Cancers ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 1660
Author(s):  
Sara Feola ◽  
Jacopo Chiaro ◽  
Beatriz Martins ◽  
Vincenzo Cerullo
Keyword(s):  
T Cell ◽  
Cancer Immunotherapy ◽  
Tumor Antigens ◽  
T Cell Response ◽  
Antigenic Peptides ◽  
T Cell Epitopes ◽  
Antigen Discovery ◽  
Future Challenges ◽  
Major Bottleneck ◽  
Therapeutic Cancer Vaccines

According to the latest available data, cancer is the second leading cause of death, highlighting the need for novel cancer therapeutic approaches. In this context, immunotherapy is emerging as a reliable first-line treatment for many cancers, particularly metastatic melanoma. Indeed, cancer immunotherapy has attracted great interest following the recent clinical approval of antibodies targeting immune checkpoint molecules, such as PD-1, PD-L1, and CTLA-4, that release the brakes of the immune system, thus reviving a field otherwise poorly explored. Cancer immunotherapy mainly relies on the generation and stimulation of cytotoxic CD8 T lymphocytes (CTLs) within the tumor microenvironment (TME), priming T cells and establishing efficient and durable anti-tumor immunity. Therefore, there is a clear need to define and identify immunogenic T cell epitopes to use in therapeutic cancer vaccines. Naturally presented antigens in the human leucocyte antigen-1 (HLA-I) complex on the tumor surface are the main protagonists in evocating a specific anti-tumor CD8+ T cell response. However, the methodologies for their identification have been a major bottleneck for their reliable characterization. Consequently, the field of antigen discovery has yet to improve. The current review is intended to define what are today known as tumor antigens, with a main focus on CTL antigenic peptides. We also review the techniques developed and employed to date for antigen discovery, exploring both the direct elution of HLA-I peptides and the in silico prediction of epitopes. Finally, the last part of the review analyses the future challenges and direction of the antigen discovery field.

scholarly journals Molecular cloning, expression, purification and in silico epitope prediction of cobalamin-independent methionine synthase (Mor a 2), as a novel allergen from Morus alba pollen

2021 ◽  
Author(s):  
Yunus AKSÜT
Keyword(s):  
T Cell ◽  
B Cell ◽  
In Silico ◽  
Allergic Diseases ◽  
Structural Features ◽  
Morus Alba ◽  
Methionine Synthase ◽  
Antigenic Peptides ◽  
T Cell Epitopes ◽  
B Cell Epitopes

IntroductionMorus alba (white mulberry) pollen is an aero-allergen source that can trigger allergic diseases. Cobalamin-independent methionine synthase (MetE) in M. alba pollen has been proved to be one of the major allergens for some patients living in Istanbul (Turkey). The aim of the present study was the recombinant production and identification of MetE (Mor a 2), a novel allergen from M. alba pollen. The IgE binding reactivity of rMor a 2 produced for the first time was evaluated and some structural features were investigated by in silico methods to better understand its immunogenicity.Material and methodsThe gene encoding Mor a 2 was cloned in fission yeast, Schizosaccharomyces pombe ura4-D18h- strain, using pSLF1073 vector. This is the first report of the production of recombinant pollen allergen in S. pombe. After the purification, immunoreactivity of rMor a 2 was confirmed by immunoblotting using sera of patient allergic to M. alba pollen. Besides, B-cell epitopes of rMor a 2 were predicted using various bioinformatic tools, namely Bioinformatics Predicted Antigenic Peptides, BepiPred 2.0 and Immune Epitope Database whereas T-cell epitopes were estimated using NetMHCIIpan-3.2 and NetMHCII 2.3 servers.ResultsThe immunoblotting analysis yielded 11 of 11 positive reactions to rMor a 2. In silico predictions exerted seven B-cell epitopes (22-33, 384-394, 407-423, 547-553, 571-577, 671-678, 736-741) and seven T-cell epitopes (54-62, 161-170, 197-205, 347-358, 622-630, 657-665, 756-764).ConclusionsThese findings may help the use of rMor a 2 in the diagnosis and treatment of allergic diseases associated with M. alba and/or MetE.

scholarly journals Antigenicity of peptides comprising the immunosuppressive domain of the retroviral envelope glycoprotein

2017 ◽  
Vol 1 ◽  
pp. 22
Author(s):  
Bryony Jenkins ◽  
Urszula Eksmond ◽  
George Young ◽  
George Kassiotis
Keyword(s):  
T Cell ◽  
Envelope Glycoprotein ◽  
Cell Epitope ◽  
Lymphocyte Activation ◽  
T Cell Response ◽  
Antigenic Peptides ◽  
T Cell Epitopes ◽  
Immunosuppressive Activity ◽  
Histocompatibility Complex ◽  
Antigenic Epitopes

To achieve persistent infection of the host, viruses often subvert or suppress host immunity through mechanisms that are not entirely understood. The envelope glycoprotein of several retroviruses is thought to possess potent immunosuppressive activity, mapped to a 17-amino acid residue conserved domain. Synthetic peptides corresponding to this immunosuppressive domain can inhibit lymphocyte activation, whereas mutation of key domain residues can increase the lymphocyte response to linked antigenic epitopes. Using three T cell receptors (TCRs) of defined specificity, we examine the effect of the immunosuppressive domain on the T cell response to their respective antigenic peptides. We find that fusion of a T cell epitope to the immunosuppressive domain can greatly modulate its potency. However, the effects heavily depend on the particular combination of TCR and peptide-major histocompatibility complex class II (pMHC II), and are mimicked by sequence-scrambled peptides of similar length, suggesting they operate at the level of pMHC formation or TCR-pMHC interaction. These results offer an alternative explanation for the immunogenicity of T cell epitopes comprising the putative immunosuppressive domain, which is more consistent with an effect on peptide antigenicity than true immunosuppressive activity.

scholarly journals Antigenicity of peptides comprising the immunosuppressive domain of the retroviral envelope glycoprotein

2016 ◽  
Vol 1 ◽  
pp. 22
Author(s):  
Bryony Jenkins ◽  
Urszula Eksmond ◽  
George Young ◽  
George Kassiotis
Keyword(s):  
T Cell ◽  
Envelope Glycoprotein ◽  
Cell Epitope ◽  
Lymphocyte Activation ◽  
T Cell Response ◽  
Antigenic Peptides ◽  
T Cell Epitopes ◽  
Immunosuppressive Activity ◽  
Histocompatibility Complex ◽  
Antigenic Epitopes

To achieve persistent infection of the host, viruses often subvert or suppress host immunity through mechanisms that are not entirely understood. The envelope glycoprotein of several retroviruses is thought to possess potent immunosuppressive activity, mapped to a 17-amino acid residue conserved domain. Synthetic peptides corresponding to this immunosuppressive domain can inhibit lymphocyte activation, whereas mutation of key domain residues can increase the lymphocyte response to linked antigenic epitopes. Using three T cell receptors (TCRs) of defined specificity, we examine the effect of the immunosuppressive domain on the T cell response to their respective antigenic peptides. We find that fusion of a T cell epitope to the immunosuppressive domain can greatly modulate its potency. However, the effects heavily depend on the particular combination of TCR and peptide-major histocompatibility complex class II (pMHC II), and are mimicked by sequence-scrambled peptides of similar length, suggesting they operate at the level of TCR-pMHC interaction. These results offer an alternative explanation for the immunogenicity of T cell epitopes comprising the putative immunosuppressive domain, which is more consistent with an effect on peptide antigenicity than true immunosuppressive activity.

scholarly journals Conserved T-cell epitopes predicted by bioinformatics in SARS-COV-2 variants

2021 ◽  
Author(s):  
Feiyu Lu ◽  
Shengnan Wang ◽  
Ying Wang ◽  
Yunpeng Yao ◽  
Yangeng Wang ◽  
...  
Keyword(s):  
Amino Acid ◽  
T Cell ◽  
Hla Class I ◽  
Amino Acid Sequences ◽  
Antigenic Peptides ◽  
T Cell Epitopes ◽  
Cell Responses ◽  
Cell Immunity ◽  
Computational Workflow ◽  
High Binding Affinity

Background: Finding conservative T cell epitopes in the proteome of numerous variants of SARS-COV-2 is required to develop T cell activating SARS-COV-2 capable of inducing T cell responses against SARS-COV-2 variants. Methods: A computational workflow was performed to find HLA restricted CD8+ and CD4+ T cell epitopes among conserved amino acid sequences across the proteome of 474727 SARS-CoV-2 strains. Results: A batch of covserved regions in the amino acid sequences were found in the proteome of the SARS-COV-2 strains. 2852 and 847 peptides were predicted to have high binding affinity to distint HLA class I and class II molecules. Among them, 1456 and 484 peptides are antigenic. 392 and 111 of the antigenic peptides were found in the conseved amino acid sequences. Among the antigenic-conserved peptides, 6 CD8+ T cell epitopes and 7 CD4+ T cell epitopes were identifed. The T cell epitopes could be presented to T cells by high-affinity HLA molecules which are encoded by the HLA alleles with high population coverage. Conclusions: The T cell epitopes are conservative, antigenic and HLA presentable, and could be constructed into SARS-COV-2 vaccines for inducing protective T cell immunity against SARS-COV-2 and their variants.

scholarly journals Prediction of promiscuous T cell epitopes in RNA dependent RNA polymerase of Chikungunya virus

2017 ◽  
Vol 10 (8) ◽  
pp. 760-764 ◽  
Author(s):  
Yasir Waheed ◽  
Sher Zaman Safi ◽  
Muzammil Hasan Najmi ◽  
Hafsa Aziz ◽  
Muhammad Imran
Keyword(s):  
T Cell ◽  
Rna Polymerase ◽  
Chikungunya Virus ◽  
T Cell Epitopes ◽  
Rna Dependent Rna Polymerase
Sign in / Sign up

Export Citation Format

Share Document