A bioinformatics tool for epitope-based vaccine design that accounts for human ethnic diversity: Application to emerging infectious diseases

Oyarzún, Patricio; Ellis, Jonathan J.; Gonzalez-Galarza, Faviel F.; Jones, Andrew R.; Middleton, D.; Bodén, Mikael; Kobe, Boštjan

doi:10.1016/j.vaccine.2015.01.040

Cited by 43 publications

(33 citation statements)

References 52 publications

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“…The inclusion of T-cell epitopes in the vaccine development induces a strong and long lasting immune response and antigenic drift where antigen can easily escape the antibody memory response [19,22]. While CD8+ cytotoxic T-cells generally recognize intracellular peptides displayed by HLA class I molecules, CD4+ T-helper cells generally recognize peptides from the extracellular space, displayed by HLA class II molecules (CD4+ T-cell epitopes) [22].…”

Section: Analysis Of the Population Coveragementioning

confidence: 99%

“…They offer many of advantages such as: biosafety, selecting of conserved or immunodominant epitopes for activating cellular or humoral responses and bio-processing of these epitopes are introduced economically and rapidly. In addition, the geographic distributions of the viruses are often well defined and the ethnic populations in need of vaccination can be determined [22] Indeed, many studies showed the immunological success of peptide-based vaccines against infectious diseases in experimental animals as well as in clinical trials, which demonstrated the responses to peptide vaccines against infectious diseases, for example malaria [23][24][25][26][27] hepatitis B, and HIV infections, but unfortunately, epitope mapping using experimental methods are costly and laborious.…”

Section: Introductionmentioning

confidence: 99%

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Immunoinformatics Predication and Modelling of a Cocktail of B- and T-cells Epitopes from Envelope Glycoprotein and Nucleocapsid Proteins of Sin Nombre Virus

Ab¹,

Sm²,

S³

et al. 2017

Immunome Res

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Sin Nombre virus is a category A pathogen with a reported mortality rate ranging from 30% to 50%. It was responsible for the 2012 Yosemite National Park outbreak. Until now, Specific therapy is not available for the treatment of HCPS caused by SNV. Despite many efforts to develop safe and effective vaccines against SNV, included conventional approaches as well as molecular vaccine approaches, to date there are no vaccines proven to be highly efficacious against SNV. In our study, we analyzed envelope glycoprotein and nucleocapsid of SNV by using immunoinformatics tools housed in IEDB resources; in order to determine the most conserved and immunogenic epitopes for B-and T-cells. Then the predicted epitopes were assessed for the population coverage against the whole world population with the MHC-I and MHC-II restricted alleles. Among predicted epitopes for B-cell, the best candidates for glycoprotein and nucleocapsid were the epitope 743CKKYAYPWQT752 and the epitope 271QVDESKVS278, respectively. For glycoprotein CD8 + T cell predicted epitopes, the epitopes 208MTLPVTCFL216 and 458YTFTSLFSL466 were selected. Interestingly, the best candidates epitopes for nucleocapsid were the epitopes 25YILSFALPI133 and 239FLAARCPFL247 which had high affinity to interact with both MHC classes, I and II, and they had an excellent population coverage for Class I and II alleles throughout the world. To the best of our knowledge, our study for the first time has predicted a cocktail of B-and T-cell epitopes for designing an effective vaccine against HCPS caused by SNV

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Section: Analysis Of the Population Coveragementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immunoinformatics Predication and Modelling of a Cocktail of B- and T-cells Epitopes from Envelope Glycoprotein and Nucleocapsid Proteins of Sin Nombre Virus

Ab¹,

Sm²,

S³

et al. 2017

Immunome Res

View full text Add to dashboard Cite

show abstract

“…Consequently, identifying specific peptides or epitopes within different CFAs that induce protective antibodies and combining them into a single MEFA is an efficient means of developing a vaccine for antigenically heterogeneous pathogens like ETEC. Although this process used to be extremely tedious at best, recent advances in bioinformatic tools for epitope-based vaccine development have significantly accelerated the process (78,79).…”

Section: Etec Subunit Vaccine Candidatesmentioning

confidence: 99%

Current Progress in Developing Subunit Vaccines against Enterotoxigenic Escherichia coli-Associated Diarrhea

Zhang

Sack

2015

Clin Vaccine Immunol

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b Diarrhea continues to be a leading cause of death in children <5 years of age, and enterotoxigenic Escherichia coli (ETEC) is the most common bacterial cause of children's diarrhea. Currently, there are no available vaccines against ETEC-associated diarrhea. Whole-cell vaccine candidates have been under development but require further improvements because they provide inadequate protection and produce unwanted adverse effects. Meanwhile, a newer approach using polypeptide or subunit vaccine candidates focusing on ETEC colonization factor antigens (CFAs) and enterotoxins, the major virulence determinants of ETEC diarrhea, shows substantial promise. A conservative CFA/I adhesin tip antigen and a CFA MEFA (multiepitope fusion antigen) were shown to induce cross-reactive antiadhesin antibodies that protected against adherence by multiple important CFAs. Genetic fusion of toxoids derived from ETEC heat-labile toxin (LT) and heat-stable toxin (STa) induced antibodies neutralizing both enterotoxins. Moreover, CFA-toxoid MEFA polypeptides, generated by fusing CFA MEFA to an STa-LT toxoid fusion, induced antiadhesin antibodies that broadly inhibited adherence of the seven most important ETEC CFAs associated with about 80% of the diarrhea cases caused by ETEC strains with known CFAs. This same antigen preparation also induced antitoxin antibodies that neutralized both toxins that are associated with all cases of ETEC diarrhea. Results from these studies suggest that polypeptide or subunit vaccines have the potential to effectively protect against ETEC diarrhea. In addition, novel adhesins and mucin proteases have been investigated as potential alternatives or, more likely, additional antigens for ETEC subunit vaccine development.

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“…21 For example, while the previously described influenza virus vaccines are based on conserved epitopes, the development of a universally effective HIV-1 vaccine becomes a formidable challenge, given that this virus displays the most genetic diversity of any virus studied to date. 22 Thus, the generation of HIV-1 envelope glycoprotein (Env) immunogens that elicit neutralizing antibodies against circulating HIV-1 strains is a major goal of HIV-1 vaccine development.…”

Section: Dealing With Hiv-1 Genetic Diversitymentioning

confidence: 99%

“…These methods includes OptiTope, 44 Episopt, 45 and Predivac-2.0. 21 In addition, some algorithms have been proposed to simultaneously optimize coverage of HLA alleles (target population) and pathogen antigenic coverage. [46][47][48] Other methods for epitope-based vaccine design focus on the vaccine assembly stage of linear polypeptide constructs, aiming at improving T-cell epitope processing and to minimize junctional "neoepitopes."…”

Section: Dealing With Hiv-1 Genetic Diversitymentioning

confidence: 99%

Recombinant and epitope-based vaccines on the road to the market and implications for vaccine design and production

Oyarzún

Kobe

2015

Human Vaccines & Immunotherapeutics

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Novel vaccination approaches based on rational design of B-and T-cell epitopes -epitope-based vaccinesare making progress in the clinical trial pipeline. The epitope-focused recombinant protein-based malaria vaccine (termed RTS,S) is a next-generation approach that successfully reached phase-III trials, and will potentially become the first commercial vaccine against a human parasitic disease. Progress made on methods such as recombinant DNA technology, advanced cell-culture techniques, immunoinformatics and rational design of immunogens are driving the development of these novel concepts. Synthetic recombinant proteins comprising both B-and T-cell epitopes can be efficiently produced through modern biotechnology and bioprocessing methods, and can enable the induction of large repertoires of immune specificities. In particular, the inclusion of appropriate CD4+ T-cell epitopes is increasingly considered a key vaccine component to elicit robust immune responses, as suggested by results coming from HIV-1 clinical trials. In silico strategies for vaccine design are under active development to address genetic variation in pathogens and several broadly protective "universal" influenza and HIV-1 vaccines are currently at different stages of clinical trials. Other methods focus on improving population coverage in target populations by rationally considering specificity and prevalence of the HLA proteins, though a proof-of-concept in humans has not been demonstrated yet. Overall, we expect immunoinformatics and bioprocessing methods to become a central part of the next-generation epitope-based vaccine development and production process.

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A bioinformatics tool for epitope-based vaccine design that accounts for human ethnic diversity: Application to emerging infectious diseases

Cited by 43 publications

References 52 publications

Immunoinformatics Predication and Modelling of a Cocktail of B- and T-cells Epitopes from Envelope Glycoprotein and Nucleocapsid Proteins of Sin Nombre Virus

Immunoinformatics Predication and Modelling of a Cocktail of B- and T-cells Epitopes from Envelope Glycoprotein and Nucleocapsid Proteins of Sin Nombre Virus

Current Progress in Developing Subunit Vaccines against Enterotoxigenic Escherichia coli-Associated Diarrhea

Recombinant and epitope-based vaccines on the road to the market and implications for vaccine design and production

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