scholarly journals Computational assembly of a human Cytomegalovirus vaccine upon experimental epitope legacy

2019 ◽  
Vol 20 (S6) ◽  
Author(s):  
Monica J. Quinzo ◽  
Esther M. Lafuente ◽  
Pilar Zuluaga ◽  
Darren R. Flower ◽  
Pedro A. Reche
Keyword(s):  
T Cell ◽  
B Cell ◽  
Human Cytomegalovirus ◽  
Cd4 T Cell ◽  
World Population ◽  
T Cell Epitopes ◽  
Cell Component ◽  
Universal Vaccine ◽  
Cell Responses ◽  
Immunosuppressed Patients

Abstract Background Human Cytomegalovirus (HCMV) is a ubiquitous herpesvirus affecting approximately 90% of the world population. HCMV causes disease in immunologically naive and immunosuppressed patients. The prevention, diagnosis and therapy of HCMV infection are thus crucial to public health. The availability of effective prophylactic and therapeutic treatments remain a significant challenge and no vaccine is currently available. Here, we sought to define an epitope-based vaccine against HCMV, eliciting B and T cell responses, from experimentally defined HCMV-specific epitopes. Results We selected 398 and 790 experimentally validated HCMV-specific B and T cell epitopes, respectively, from available epitope resources and apply a knowledge-based approach in combination with immunoinformatic predictions to ensemble a universal vaccine against HCMV. The T cell component consists of 6 CD8 and 6 CD4 T cell epitopes that are conserved among HCMV strains. All CD8 T cell epitopes were reported to induce cytotoxic activity, are derived from early expressed genes and are predicted to provide population protection coverage over 97%. The CD4 T cell epitopes are derived from HCMV structural proteins and provide a population protection coverage over 92%. The B cell component consists of just 3 B cell epitopes from the ectodomain of glycoproteins L and H that are highly flexible and exposed to the solvent. Conclusions We have defined a multiantigenic epitope vaccine ensemble against the HCMV that should elicit T and B cell responses in the entire population. Importantly, although we arrived to this epitope ensemble with the help of computational predictions, the actual epitopes are not predicted but are known to be immunogenic.

scholarly journals Designing of multiepitope-based vaccine against Leptospirosis using Immuno-Informatics approaches

2021 ◽  
Author(s):  
Mohd Abdullah ◽  
Mohammad Kadivella ◽  
Rolee Sharma ◽  
Syed M. Faisal ◽  
Sarwar Azam
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cellular Localization ◽  
Tertiary Structure ◽  
Vaccine Candidate ◽  
Surface Proteins ◽  
World Population ◽  
T Cell Epitopes ◽  
Universal Vaccine ◽  
Vaccine Candidates

AbstractLeptospira is a zoonotic pathogen causing significant morbidity and mortality both in animals and humans. Although several surface proteins have been identified as vaccine candidate, they failed to induce sterilizing immunity and cross protection against different serovars. Thus, identification of highly immunogenic antigens that are conserved among pathogenic serovars would be first step towards development of universal vaccine for Leptospirosis. Here we used reverse vaccinology pipeline to screen core genome of pathogenic Leptospira spp.in order to identify suitable vaccine candidates. Based on properties like sub cellular localization, adhesin, homology to human proteins, antigenicity and allergenicity, 18 antigenic proteins were identified and were further investigated for immunological properties. Based on immunogenicity, Protegenicity, Antigenicity, B-cell and promiscuous T-cell epitopes, 6 Potential Vaccine Candidates (PVCs) were finally selected which covered most of the affected world population. For designing a Multi-Epitope Vaccine (MEV), 6 B-cell and 6 promiscuous MHC-I and MHC-II epitopes from each candidate were clustered with linkers in between and stitched along with a TLR4 adjuvant (APPHALS) at the N-terminal to form a construct of 361 amino acids. The physiochemical properties, secondary and tertiary structure analysis revealed that MEV was highly stable. Molecular docking analysis revealed the deep binding interactions of the MEV construct within the grooves of human TLR4 (4G8A). In-silico codon optimization and cloning of the vaccine construct assured good expression. Further, immune simulations have shown that MEV could induce strong and diverse B and T cell responses. Taken together our results indicate that the designed MEV could be a promising subunit vaccine candidate against Leptospirosis, however it requires experimental validation.

Major contribution of codominant CD8 and CD4 T cell epitopes to the human cytomegalovirus-specific T cell repertoire

2005 ◽  
Vol 62 (1) ◽  
pp. 77-86 ◽  
Author(s):  
M. -D. Nastke† ◽  
L. Herrgen† ◽  
S. Walter ◽  
D. Wernet ◽  
H. -G. Rammensee ◽  
...  
Keyword(s):  
T Cell ◽  
Human Cytomegalovirus ◽  
Cd4 T Cell ◽  
T Cell Epitopes ◽  
T Cell Repertoire ◽  
Cell Repertoire

scholarly journals Enhanced T- and B-cell responses to simian immunodeficiency virus (SIV)agm, SIVmac and human immunodeficiency virus type 1 Gag DNA immunization and identification of novel T-cell epitopes in mice via codon optimization

2009 ◽  
Vol 90 (10) ◽  
pp. 2513-2518 ◽  
Author(s):  
Christine S. Siegismund ◽  
Oliver Hohn ◽  
Reinhard Kurth ◽  
Stephen Norley
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
B Cell ◽  
Simian Immunodeficiency Virus ◽  
Codon Optimization ◽  
T Cell Epitopes ◽  
Gm Csf ◽  
Cell Responses ◽  
Immunodeficiency Virus

As a prelude to primate studies, the immunogenicity of wild-type and codon-optimized versions of simian immunodeficiency virus (SIV)agm Gag DNA, with and without co-administered granulocyte–macrophage colony-stimulating factor (GM-CSF) DNA, was directly compared in two strains of mice. Gag-specific T cells in the splenocytes of BALB/c and C57BL/6 mice immunized by gene gun were quantified by ELISpot using panels of overlapping synthetic peptides (15mers) spanning the entire capsid proteins of SIVagm, SIVmac and human immunodeficiency virus type 1. Specific antibodies were measured by ELISA. Codon optimization was shown to significantly increase the immune response to the DNA immunogens, reducing the amount of DNA necessary to induce cellular and antibody responses by one and two orders of magnitude, respectively. Co-administration of murine GM-CSF DNA was necessary for the induction of high level T- and B-cell responses. Finally, it was possible to identify both known and novel T-cell epitopes in the Gag proteins of the three viruses.

scholarly journals Single cell profiling of T and B cell repertoires following SARS-CoV-2 mRNA vaccine

2021 ◽  
Author(s):  
Suhas Sureshchandra ◽  
Sloan A. Lewis ◽  
Brianna Doratt ◽  
Allen Jankeel ◽  
Izabela Ibraim ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cell ◽  
Single Cell ◽  
Cd8 T Cells ◽  
Natural Infection ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
Cd4 T Cell ◽  
Cell Responses

mRNA based vaccines for SARS-CoV-2 have shown exceptional clinical efficacy providing robust protection against severe disease. However, our understanding of transcriptional and repertoire changes following full vaccination remains incomplete. We used single-cell RNA sequencing and functional assays to compare humoral and cellular responses to two doses of mRNA vaccine with responses observed in convalescent individuals with asymptomatic disease. Our analyses revealed enrichment of spike-specific B cells, activated CD4 T cells, and robust antigen-specific polyfunctional CD4 T cell responses in all vaccinees. On the other hand, CD8 T cell responses were both weak and variable. Interestingly, clonally expanded CD8 T cells were observed in every vaccinee, as observed following natural infection. TCR gene usage, however, was variable, reflecting the diversity of repertoires and MHC polymorphism in the human population. Natural infection induced expansion of larger CD8 T cell clones occupied distinct clusters, likely due to the recognition of a broader set of viral epitopes presented by the virus not seen in the mRNA vaccine. Our study highlights a coordinated adaptive immune response where early CD4 T cell responses facilitate the development of the B cell response and substantial expansion of effector CD8 T cells, together capable of contributing to future recall responses.

scholarly journals CD4 + T Cell‐Released Extracellular Vesicles Potentiate the Efficacy of the HBsAg Vaccine by Enhancing B Cell Responses

2019 ◽  
Vol 6 (23) ◽  
pp. 1802219 ◽  
Author(s):  
Jian Lu ◽  
Jing Wu ◽  
Feiting Xie ◽  
Jie Tian ◽  
Xinyi Tang ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Extracellular Vesicles ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
B Cell Responses

scholarly journals Human Cytomegalovirus Differentially Controls B Cell and T Cell Responses through Effects on Plasmacytoid Dendritic Cells

2007 ◽  
Vol 179 (11) ◽  
pp. 7767-7776 ◽  
Author(s):  
Stefania Varani ◽  
Madeleine Cederarv ◽  
Sari Feld ◽  
Charlotte Tammik ◽  
Giada Frascaroli ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
B Cell ◽  
Human Cytomegalovirus ◽  
T Cell Responses ◽  
Plasmacytoid Dendritic Cells ◽  
Cell Responses

scholarly journals Computer-Aided Design of an Epitope-Based Vaccine against Epstein-Barr Virus

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Julio Alonso-Padilla ◽  
Esther M. Lafuente ◽  
Pedro A. Reche
Keyword(s):  
T Cell ◽  
B Cell ◽  
Epstein Barr Virus ◽  
Cell Epitope ◽  
T Cell Epitopes ◽  
Cell Component ◽  
B Cell Epitopes ◽  
Barr Virus ◽  
Epstein Barr ◽  
Epitope Selection

Epstein-Barr virus is a very common human virus that infects 90% of human adults. EBV replicates in epithelial and B cells and causes infectious mononucleosis. EBV infection is also linked to various cancers, including Burkitt’s lymphoma and nasopharyngeal carcinomas, and autoimmune diseases such as multiple sclerosis. Currently, there are no effective drugs or vaccines to treat or prevent EBV infection. Herein, we applied a computer-aided strategy to design a prophylactic epitope vaccine ensemble from experimentally defined T and B cell epitopes. Such strategy relies on identifying conserved epitopes in conjunction with predictions of HLA presentation for T cell epitope selection and calculations of accessibility and flexibility for B cell epitope selection. The T cell component includes 14 CD8 T cell epitopes from early antigens and 4 CD4 T cell epitopes, targeted during the course of a natural infection and providing a population protection coverage of over 95% and 81.8%, respectively. The B cell component consists of 3 experimentally defined B cell epitopes from gp350 plus 4 predicted B cell epitopes from other EBV envelope glycoproteins, all mapping in flexible and solvent accessible regions. We discuss the rationale for the formulation and possible deployment of this epitope vaccine ensemble.

scholarly journals Identification of key peptide-specific CD4+T cell responses to human cytomegalovirus: implications for tracking antiviral populations

2006 ◽  
Vol 146 (2) ◽  
pp. 203-210 ◽  
Author(s):  
G. C. Harcourt ◽  
T. J. Scriba ◽  
N. Semmo ◽  
S. Bounds ◽  
E. Taylor ◽  
...  
Keyword(s):  
T Cell ◽  
Human Cytomegalovirus ◽  
T Cell Responses ◽  
Cd4 T Cell ◽  
Cell Responses

scholarly journals Design of Peptide Vaccine for COVID19: CD8+ and CD4+ T cell epitopes from SARS-CoV-2 open-reading-frame protein variants

2021 ◽  
Author(s):  
Simone Parn ◽  
Gabriel Jabbour ◽  
Vincent Nguyenkhoa ◽  
Sivanesan Dakshanamurthy
Keyword(s):  
T Cell ◽  
Vaccine Development ◽  
Human Life ◽  
Peptide Vaccine ◽  
T Cell Response ◽  
Cd4 T Cell ◽  
World Population ◽  
T Cell Epitopes ◽  
The World ◽  
Potential Vaccine

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, has challenged public health at an unprecedented scale which has led to a dramatic loss of human life worldwide. To design a protective vaccine against SARS-CoV-2, it is necessary to understand which SARS-CoV-2 specific epitopes can elicit a T cell response and provide protection across a broad population. In this study, PLpro and RdRp, two immunogenic non-structural proteins from an immunodominant gene region ORF1ab, as well as ORF3a and ORF9b are identified as potential vaccine targets against SARS-CoV-2. To select top epitopes for vaccine design, we used various clinical properties, such as antigenicity, allergenicity, toxicity and IFN-y secretion. The analysis of CD8 and CD4 T cell epitopes revealed multiple potential vaccine constructs that cover a high percentage of the world population. We identified 8 immunogenic, antigenic, non-allergenic, non-toxic, stable and IFN-y inducing CD8 proteins for nsp3, 4 for nsp12, 11 for ORF3a and 3 for ORF9b that are common across four lineages of variants of concern: B.1.1.7, P.1, B.1.351 and B.1.617.2, which protect 98.12%, 87.08%, 96.07% and 63.8% of the world population, respectively. We also identified variant specific T cell epitopes that could be useful in targeting each variant strain separately. Including the prediction of mouse MHC affinity towards our top CD8 epitopes, our study revealed a total of 3 immunogenic, antigenic, non-allergenic, non-toxic, stable and IFN-y inducing CD8 epitopes overlapping with 6 antigenic, non-allergenic, non-toxic, stable and IFN-y inducing CD4 epitopes across all four variants of concern which can effectively be utilized in pre-clinical studies. The landscape of SARS-CoV-2 T cell epitopes that we identified can help lead SARS-CoV-2 vaccine development as well as epitope-based peptide vaccine research in the future.

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