In silico study to predict promiscuous T cell and B cell-epitopes derived from the vaccine candidate antigens of Plasmodium vivax binding to MHC class-II alleles

Giardiasis is one of the most common gastrointestinal infections worldwide, mainly in developing countries. The etiological agent is the Giardia lamblia parasite. Giardiasis mainly affects children and immunocompromised people, causing symptoms such as diarrhea, dehydration, abdominal cramps, nausea, and malnutrition. In order to develop an effective vaccine against giardiasis, it is necessary to understand the host-Giardia interactions, the immunological mechanisms involved in protection against infection, and to characterize the parasite antigens that activate the host immune system. In this study, we identify and characterize potential T-cell and B-cell epitopes of Giardia immunogenic proteins by immunoinformatic approaches, and we discuss the potential role of those epitopes to stimulate the host´s immune system. We selected the main immunogenic and protective proteins of Giardia experimentally investigated. We predicted T-cell and B-cell epitopes using immunoinformatic tools (NetMHCII and BCPREDS). Variable surface proteins (VSPs), structural (giardins), metabolic, and cyst wall proteins were identified as the more relevant immunogens of G. lamblia. We described the protein sequences with the highest affinity to bind MHC class II molecules from mouse (I-Ak and I-Ad) and human (DRB1*03:01 and DRB1*13:01) alleles, as well as we selected promiscuous epitopes, which bind to the most common range of MHC class II molecules in human population. In addition, we identified the presence of conserved epitopes within the main protein families (giardins, VSP, CWP) of Giardia. To our knowledge, this is the first in silico study that analyze immunogenic proteins of G. lamblia by combining bioinformatics strategies to identify potential T-cell and B-cell epitopes, which can be potential candidates in the development of peptide-based vaccines. The bioinformatics analysis demonstrated in this study provides a deeper understanding of the Giardia immunogens that bind to critical molecules of the host immune system, such as MHC class II and antibodies, as well as strategies to rational design of peptide-based vaccine against giardiasis.

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Structural modeling and conserved epitopes prediction against SARS-COV-2 structural proteins for vaccine development

10.21203/rs.2.23973/v1 ◽

2020 ◽

Cited By ~ 3

Author(s):

Muhammad Tahir ul Qamar ◽

Farah Shahid ◽

Usman Ali Ashfaq ◽

Sidra Aslam ◽

Israr Fatima ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

Mhc Class I ◽

Mhc Class Ii ◽

Class Ii ◽

Class I ◽

Structural Proteins ◽

Severe Illness ◽

T Cell Epitopes ◽

B Cell Epitopes

Abstract Background: Coronavirus disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Corona virus 2 (SARS-COV-2) was first diagnosed in December 2019, Wuhan, China. Little is known about this new virus and it has the potential to cause severe illness and pneumonia in some people, therefore the development of an effective vaccine is highly desired.Methods: Immunoinformatics and statistical approaches were used in this study to forecast B- and T- cell epitopes for the SARS-COV-2 structural proteins (Surface glycoprotein, Envelope protein, and Membrane glycoprotein) that may play a key role in eliciting immune response against COVID-19. Different types of B cell epitopes (linear as well as discontinuous) and T cell (MHC class I and MHC class II) were determined. Moreover, their antigenicity and allergenicity were also estimated.Results: The antigenic B-cell epitopes exposed to the outer surface were screened out and 23 linear B cell epitopes were selected. “SPTKLNDLCFTNVY” had the highest antigenicity score among B cell epitopes. The T-cell epitopes bound to multiple alleles, antigenic, non-allergen, non-toxic, and conserved in the protein sequence were shortlisted. In total, 16 epitopes (9 from MHC class I and 7 from MHC class II) were selected. Among the T-cell epitopes, MHC class I (IPFAMQMAYRFN) and MHC class II (VTLACFVLAAVYRIN) were classified as strongly antigenic. Digestion analysis verified the safety and stability of the peptides predicted during this study. Furthermore, docking analyses of predicted peptides showed significant interactions with the HLA-B7 allele.Conclusion: The putative antigen epitopes identified in this study may serve as vaccine candidates and can help to eliminate/control growing health threat of COVID-19.

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Faculty Opinions recommendation of Cutting edge: Conditional MHC class II expression reveals a limited role for B cell antigen presentation in primary and secondary CD4 T cell responses.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718020496.793480946 ◽

2013 ◽

Author(s):

Tim Manser

Keyword(s):

T Cell ◽

B Cell ◽

Antigen Presentation ◽

Mhc Class Ii ◽

T Cell Responses ◽

Class Ii ◽

Cutting Edge ◽

Cd4 T Cell ◽

Cell Antigen ◽

Cell Responses

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In silico prediction of T‐cell and B‐cell epitopes of human papillomavirus type 16 L1 protein

Biotechnology and Applied Biochemistry ◽

10.1002/bab.2128 ◽

2021 ◽

Author(s):

Shahab Mahmoudvand ◽

Somayeh Shokri ◽

Manoochehr Makvandi ◽

Reza Taherkhani ◽

Mohammad Rashno ◽

...

Keyword(s):

Human Papillomavirus ◽

T Cell ◽

B Cell ◽

In Silico ◽

In Silico Prediction ◽

B Cell Epitopes ◽

Human Papillomavirus Type 16 ◽

L1 Protein

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Epitope‐based peptide vaccine design and target site depiction against Middle East Respiratory Syndrome Coronavirus: an immune-informatics study

Journal of Translational Medicine ◽

10.1186/s12967-019-2116-8 ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 43

Author(s):

Muhammad Tahir ul Qamar ◽

Saman Saleem ◽

Usman Ali Ashfaq ◽

Amna Bari ◽

Farooq Anwar ◽

...

Keyword(s):

T Cell ◽

Middle East ◽

B Cell ◽

Mhc Class Ii ◽

Peptide Vaccine ◽

Middle East Respiratory Syndrome ◽

T Cell Epitopes ◽

Resistance Response ◽

B Cell Epitopes ◽

S Protein

Abstract Background Middle East Respiratory Syndrome Coronavirus (MERS-COV) is the main cause of lung and kidney infections in developing countries such as Saudi Arabia and South Korea. This infectious single-stranded, positive (+) sense RNA virus enters the host by binding to dipeptidyl-peptide receptors. Since no vaccine is yet available for MERS-COV, rapid case identification, isolation, and infection prevention strategies must be used to combat the spreading of MERS-COV infection. Additionally, there is a desperate need for vaccines and antiviral strategies. Methods The present study used immuno-informatics and computational approaches to identify conserved B- and T cell epitopes for the MERS-COV spike (S) protein that may perform a significant role in eliciting the resistance response to MERS-COV infection. Results Many conserved cytotoxic T-lymphocyte epitopes and discontinuous and linear B-cell epitopes were predicted for the MERS-COV S protein, and their antigenicity and interactions with the human leukocyte antigen (HLA) B7 allele were estimated. Among B-cell epitopes, QLQMGFGITVQYGT displayed the highest antigenicity-score, and was immensely immunogenic. Among T-cell epitopes, MHC class-I peptide YKLQPLTFL and MHC class-II peptide YCILEPRSG were identified as highly antigenic. Furthermore, docking analyses revealed that the predicted peptides engaged in strong bonding with the HLA-B7 allele. Conclusion The present study identified several MERS-COV S protein epitopes that are conserved among various isolates from different countries. The putative antigenic epitopes may prove effective as novel vaccines for eradication and combating of MERS-COV infection.

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A Superantigen-Antibody Fusion Protein for T-Cell Immunotherapy of Human B-Lineage Malignancies

Blood ◽

10.1182/blood.v89.6.2089 ◽

1997 ◽

Vol 89 (6) ◽

pp. 2089-2097 ◽

Cited By ~ 21

Author(s):

Cecilia Gidlöf ◽

Mikael Dohlsten ◽

Peter Lando ◽

Terje Kalland ◽

Christer Sundström ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Fusion Protein ◽

B Cell ◽

Binding Affinity ◽

Mhc Class Ii ◽

Class Ii ◽

Target Cells ◽

Cell Based Therapy ◽

B Lineage

Abstract The bacterial superantigen staphylococcal enterotoxin A (SEA) is an efficient activator of cytotoxic T cells when presented on major histocompatibility complex (MHC) class II molecules of target cells. Our previous studies showed that such SEA-directed T cells efficiently lysed chronic B-lymphocytic leukemia (B-CLL) cells. Next, we made a mutated SEA–protein A (SEAm-PA) fusion protein with more than 1,000-fold reduced binding affinity for MHC class II compared with native SEA. The fusion protein was successfully used to direct T cells to B-CLL cells coated with different B lineage–directed monoclonal antibodies (MoAbs). In this communication, we constructed a recombinant anti-CD19-Fab-SEAm fusion protein. The MHC class II binding capacity of the SEA part was drastically reduced by a D227A point mutation, whereas the T-cell activation properties were retained. The Fab part of the fusion protein displayed a binding affinity for CD19+ cells in the nanomolar range. The anti-CD19-Fab-SEAm molecule mediated effective, specific, rapid, and perforin-like T-cell lysis of B-CLL cells at low effector to target cell ratios. Normal CD19+ B cells were sensitive to lysis, whereas CD34+ progenitor cells and monocytes/macrophages were resistant. A panel of CD19+ B-cell lines representing different B-cell developmental stages were efficiently lysed, and the sensitivity correlated with surface ICAM-1 expression. The anti-CD19-Fab-SEAm fusion protein mediated highly effective killing of tumor biopsy cells representing several types of B-cell non-Hodgkin's lymphoma (B-NHL). Humanized severe combined immune deficiency (SCID) mice carrying Daudi lymphoma cells were used as an in vivo therapy model for evaluation of the anti-CD19-Fab-SEAm fusion protein. Greater than 90% reduction in tumor weight was recorded in anti-CD19-Fab-SEAm–treated animals compared with control animals receiving an irrelevant Fab-SEAm fusion protein. The present results indicate that MoAb-targeted superantigens (SAgs) may represent a promising approach for T-cell–based therapy of CD19+ B-cell malignancies.

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Exosomes isolated from a murine B cell line present antigen to an MHC class II restricted T cell hybridoma

Immunology Letters ◽

10.1016/s0165-2478(97)85959-7 ◽

1997 ◽

Vol 56 ◽

pp. 241

Author(s):

D.H. Schuurhuis ◽

M.J. Kleijmeer ◽

M.L.H. de Bruijn ◽

H.J. Geuze ◽

C.J.M. Melief

Keyword(s):

T Cell ◽

B Cell ◽

Cell Line ◽

Mhc Class Ii ◽

Class Ii

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Immuno-informatics Design of a Multimeric Epitope Peptide Based Vaccine Targeting SARS-CoV-2 Spike Glycoprotein

10.1101/2020.07.30.228221 ◽

2020 ◽

Author(s):

Onyeka S. Chukwudozie ◽

Clive M. Gray ◽

Tawakalt A. Fagbayi ◽

Rebecca C. Chukwuanukwu ◽

Victor O. Oyebanji ◽

...

Keyword(s):

T Cell ◽

B Cell ◽

In Silico ◽

Peptide Vaccine ◽

Spike Protein ◽

Cell Mediated Immunity ◽

Epitope Peptide ◽

Mhc I ◽

B Cell Epitopes ◽

Antibody Recognition

ABSTRACTDeveloping an efficacious vaccine to SARS-CoV-2 infection is critical to stem COVID-19 fatalities and providing the global community with immune protection. We have used a bioinformatic approach to aid in the design of an epitope peptide-based vaccine against the spike protein of the virus. Five antigenic B cell epitopes with viable antigenicity and a total of 27 discontinuous B cell epitopes were mapped out structurally in the spike protein for antibody recognition. We identified eight CD8+ T cell 9-mers along with 12 CD4+ T cell 14-15-mer as promising candidate epitopes putatively restricted by a large number of MHC-I and II alleles respectively. We used this information to construct an in silico chimeric peptide vaccine whose translational rate was highly expressed when cloned in pET28a (+) vector. The vaccine construct was predicted to elicit high antigenicity and cell-mediated immunity when given as a homologous prime-boost, with triggering of toll-like receptor 5 by the adjuvant linker. The vaccine was characterized by an increase in IgM and IgG and an array of Th1 and Th2 cytokines. Upon in silico challenge with SARS-CoV-2, there was a decrease in antigen levels using our immune simulations. We therefore propose that potential vaccine designs consider this approach.

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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

Archives of Medical Science ◽

10.5114/aoms/136322 ◽

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.

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