scholarly journals Identification of highly conserved, serotype-specific dengue virus sequences: implications for vaccine design

BMC Genomics ◽  
2019 ◽  
Vol 20 (S9) ◽  
Author(s):  
Li Chuin Chong ◽  
Asif M. Khan
Keyword(s):  
T Cell ◽  
Dengue Virus ◽  
Large Scale ◽  
Target Selection ◽  
Vaccine Design ◽  
Effective Vaccine ◽  
Amino Acid Difference ◽  
Specific Response ◽  
T Cell Epitopes ◽  
Vaccine Target

Abstract Background The sequence diversity of dengue virus (DENV) is one of the challenges in developing an effective vaccine against the virus. Highly conserved, serotype-specific (HCSS), immune-relevant DENV sequences are attractive candidates for vaccine design, and represent an alternative to the approach of selecting pan-DENV conserved sequences. The former aims to limit the number of possible cross-reactive epitope variants in the population, while the latter aims to limit the cross-reactivity between the serotypes to favour a serotype-specific response. Herein, we performed a large-scale systematic study to map and characterise HCSS sequences in the DENV proteome. Methods All reported DENV protein sequence data for each serotype was retrieved from the NCBI Entrez Protein (nr) Database (txid: 12637). The downloaded sequences were then separated according to the individual serotype proteins by use of BLASTp search, and subsequently removed for duplicates and co-aligned across the serotypes. Shannon’s entropy and mutual information (MI) analyses, by use of AVANA, were performed to measure the diversity within and between the serotype proteins to identify HCSS nonamers. The sequences were evaluated for the presence of promiscuous T-cell epitopes by use of NetCTLpan 1.1 and NetMHCIIpan 3.2 server for human leukocyte antigen (HLA) class I and class II supertypes, respectively. The predicted epitopes were matched to reported epitopes in the Immune Epitope Database. Results A total of 2321 nonamers met the HCSS selection criteria of entropy < 0.25 and MI > 0.8. Concatenating these resulted in a total of 337 HCSS sequences. DENV4 had the most number of HCSS nonamers; NS5, NS3 and E proteins had among the highest, with none in the C and only one in prM. The HCSS sequences were immune-relevant; 87 HCSS sequences were both reported T-cell epitopes/ligands in human and predicted epitopes, supporting the accuracy of the predictions. A number of the HCSS clustered as immunological hotspots and exhibited putative promiscuity beyond a single HLA supertype. The HCSS sequences represented, on average, ~ 40% of the proteome length for each serotype; more than double of pan-DENV sequences (conserved across the four serotypes), and thus offer a larger choice of sequences for vaccine target selection. HCSS sequences of a given serotype showed significant amino acid difference to all the variants of the other serotypes, supporting the notion of serotype-specificity. Conclusion This work provides a catalogue of HCSS sequences in the DENV proteome, as candidates for vaccine target selection. The methodology described herein provides a framework for similar application to other pathogens.

scholarly journals Large-scale analysis of antigenic diversity of T-cell epitopes in dengue virus

2006 ◽  
Vol 7 (Suppl 5) ◽  
pp. S4 ◽  
Author(s):  
Asif M Khan ◽  
AT Heiny ◽  
Kenneth X Lee ◽  
KN Srinivasan ◽  
Tin Tan ◽  
...  
Keyword(s):  
T Cell ◽  
Dengue Virus ◽  
Large Scale ◽  
Scale Analysis ◽  
T Cell Epitopes ◽  
Antigenic Diversity ◽  
Large Scale Analysis

scholarly journals Towards large-scale identification of HLA-restricted T cell epitopes from four vaccine candidate antigens in a malaria endemic community in Ghana

Vaccine ◽  
2021 ◽  
Author(s):  
Kwadwo Asamoah Kusi ◽  
Ebenezer Addo Ofori ◽  
Kwadwo Akyea-Mensah ◽  
Eric Kyei-Baafour ◽  
Augustina Frimpong ◽  
...  
Keyword(s):  
T Cell ◽  
Large Scale ◽  
Vaccine Candidate ◽  
T Cell Epitopes

Immune responses of seven different “promiscuous” T-cell epitopes on chimeric peptide vaccine design

Peptides ◽  
1994 ◽  
pp. 732-733 ◽  
Author(s):  
A. M. DiGeorge ◽  
B. Wang ◽  
S. F. Kobs-Conrad ◽  
P. T. P. Kaumaya
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Peptide Vaccine ◽  
Vaccine Design ◽  
T Cell Epitopes ◽  
Chimeric Peptide

scholarly journals Immunoinformatics and Structural Analysis for Identification of Immunodominant Epitopes in SARS-CoV-2 as Potential Vaccine Targets

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 290 ◽  
Author(s):  
Sumit Mukherjee ◽  
Dmitry Tworowski ◽  
Rajesh Detroja ◽  
Sunanda Biswas Mukherjee ◽  
Milana Frenkel-Morgenstern
Keyword(s):  
Peptide Vaccine ◽  
Vaccine Design ◽  
Computational Prediction ◽  
Effective Vaccine ◽  
Cell Mediated Immunity ◽  
T Cell Epitopes ◽  
Protective Antigens ◽  
Global Pandemic ◽  
Time Required ◽  
Immunodominant Epitopes

A new coronavirus infection, COVID-19, has recently emerged, and has caused a global pandemic along with an international public health emergency. Currently, no licensed vaccines are available for COVID-19. The identification of immunodominant epitopes for both B- and T-cells that induce protective responses in the host is crucial for effective vaccine design. Computational prediction of potential epitopes might significantly reduce the time required to screen peptide libraries as part of emergent vaccine design. In our present study, we used an extensive immunoinformatics-based approach to predict conserved immunodominant epitopes from the proteome of SARS-CoV-2. Regions from SARS-CoV-2 protein sequences were defined as immunodominant, based on the following three criteria regarding B- and T-cell epitopes: (i) they were both mapped, (ii) they predicted protective antigens, and (iii) they were completely identical to experimentally validated epitopes of SARS-CoV. Further, structural and molecular docking analyses were performed in order to understand the binding interactions of the identified immunodominant epitopes with human major histocompatibility complexes (MHC). Our study provides a set of potential immunodominant epitopes that could enable the generation of both antibody- and cell-mediated immunity. This could contribute to developing peptide vaccine-based adaptive immunotherapy against SARS-CoV-2 infections and prevent future pandemic outbreaks.

scholarly journals Potent HIV-1-Specific CD8 T Cell Responses Induced in Mice after Priming with a Multiepitopic DNA-TMEP and Boosting with the HIV Vaccine MVA-B

Viruses ◽  
2018 ◽  
Vol 10 (8) ◽  
pp. 424 ◽  
Author(s):  
Beatriz Perdiguero ◽  
Suresh C. Raman ◽  
Cristina Sánchez-Corzo ◽  
Carlos Oscar S. Sorzano ◽  
José Ramón Valverde ◽  
...  
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Effective Vaccine ◽  
T Cell Epitopes ◽  
Cell Responses ◽  
Modified Vaccinia Virus Ankara ◽  
Hiv 1

An effective vaccine against Human Immunodeficiency Virus (HIV) still remains the best solution to provide a sustainable control and/or eradication of the virus. We have previously generated the HIV-1 vaccine modified vaccinia virus Ankara (MVA)-B, which exhibited good immunogenicity profile in phase I prophylactic and therapeutic clinical trials, but was unable to prevent viral rebound after antiretroviral (ART) removal. To potentiate the immunogenicity of MVA-B, here we described the design and immune responses elicited in mice by a new T cell multi-epitopic B (TMEP-B) immunogen, vectored by DNA, when administered in homologous or heterologous prime/boost regimens in combination with MVA-B. The TMEP-B protein contained conserved regions from Gag, Pol, and Nef proteins including multiple CD4 and CD8 T cell epitopes functionally associated with HIV control. Heterologous DNA-TMEP/MVA-B regimen induced higher HIV-1-specific CD8 T cell responses with broader epitope recognition and higher polyfunctional profile than the homologous DNA-TMEP/DNA-TMEP or the heterologous DNA-GPN/MVA-B combinations. Moreover, higher HIV-1-specific CD4 and Tfh immune responses were also detected using this regimen. After MVA-B boost, the magnitude of the anti-VACV CD8 T cell response was significantly compromised in DNA-TMEP-primed animals. Our results revealed the immunological potential of DNA-TMEP prime/MVA-B boost regimen and supported the application of these combined vectors in HIV-1 prevention and/or therapy.

scholarly journals Dengue virus-infected human dendritic cells reveal hierarchies of naturally expressed novel NS3 CD8 T cell epitopes

2014 ◽  
Vol 177 (3) ◽  
pp. 696-702 ◽  
Author(s):  
P. Piazza ◽  
D. Campbell ◽  
E. Marques ◽  
W. H. Hildebrand ◽  
R. Buchli ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
T Cell ◽  
Dengue Virus ◽  
Cd8 T Cell ◽  
T Cell Epitopes ◽  
Human Dendritic Cells

scholarly journals Physical Linkage of Naturally Complexed Bacterial Outer Membrane Proteins Enhances Immunogenicity

2007 ◽  
Vol 76 (3) ◽  
pp. 1223-1229 ◽  
Author(s):  
Henriette Macmillan ◽  
Junzo Norimine ◽  
Kelly A. Brayton ◽  
Guy H. Palmer ◽  
Wendy C. Brown
Keyword(s):  
T Cell ◽  
Membrane Proteins ◽  
Outer Membrane ◽  
Outer Membrane Proteins ◽  
Surface Protein ◽  
Host Cells ◽  
Effective Vaccine ◽  
T Cell Epitopes ◽  
Carrier Effect ◽  
Major Surface

ABSTRACTThe outer membrane proteins (OMPs) of bacterial pathogens are essential for their growth and survival and especially for attachment and invasion of host cells. Since the outer membrane is the interface between the bacterium and the host cell, outer membranes and individual OMPs are targeted for development of vaccines against many bacterial diseases. Whole outer membrane fractions often protect against disease, and this protection cannot be fully reproduced by using individual OMPs. Exactly how the interactions among individual OMPs influence immunity is not well understood. We hypothesized that one OMP rich in T-cell epitopes can act as a carrier for an associated OMP which is poor in T-cell epitopes to generate T-dependent antibody responses, similar to the hapten-carrier effect. Major surface protein 1a (MSP1a) and MSP1b1 occur as naturally complexed OMPs in theAnaplasma marginaleouter membrane. Previous studies demonstrated that immunization with the native MSP1 heteromer induced strong immunoglobulin G (IgG) responses to both proteins, but only MSP1a stimulated strong CD4+T-cell responses. Therefore, to test our hypothesis, constructs of CD4+T-cell epitopes from MSP1a linked to MSP1b1 were compared with individually administered MSP1a and MSP1b1 for induction of MSP1b-specific IgG. By linking the T-cell epitopes from MSP1a to MSP1b1, significantly higher IgG titers against MSP1b1 were induced. Understanding how the naturally occurring intermolecular interactions between OMPs influence the immune response may lead to more effective vaccine design.

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