Development of Epitope-Based Peptide Vaccine

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Vaccine Adjuvants".

Deadline for manuscript submissions: closed (31 May 2022) | Viewed by 23319

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Department of Veterinary Medicine, University Aldo Moro of Bari, Sp Casamassima Km 3, Valenzano, 70010 Bari, Italy
Interests: coronaviruses; viral enteritis; respiratory and genital diseases
Special Issues, Collections and Topics in MDPI journals
Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA 99164-7040, USA
Interests: blood parasite; transmission blocking vaccine; Babesia; Transfection; vector born diseases; ticks; genetic markers; vaccines
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,  

This Special Issue focuses on the development of epitope-based peptide vaccines. Since efficient recombinant protein and synthetic peptide production systems were created, there have been many published vaccine trials using single or multiple full-length recombinant protein(s) and peptides with variable results. However, the number of epitope-based vaccines remains limited. Full length recombinant protein-based vaccines may fail due to many reasons. Some of these failures could be related to the structural, conformational, and biochemical differences among the recombinant protein vs. the original native versions of the proteins. In addition, there is variability in the immune responses among protein’s epitopes after vaccination due to host MHC restriction, and differences in the degree of immunodominance among distinct protein epitopes. Thus, identification of immunodominant B- and T-cell epitopes is crucial to induce protective responses in the host upon vaccination. Moreover, immunoinformatics-based approaches, depending on in silico prediction of potential epitopes, may significantly reduce the time required to screen peptide libraries to discover immunodominant epitopes. Here, we are trying to shed light on the importance of epitope-based peptide vaccine strategies as alternative approaches, which may help to improve vaccine efficacy.

This Special Issue of Vaccines aims to cover topics relevant to epitope-based peptide vaccine design. We are pleased to invite you to submit an original research or review article discussing this topic. We are looking forward to publishing your interesting inputs and original insights in this field of research.

Prof. Dr. Maria Tempesta
Dr. Heba Alzan
Guest Editors

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Keywords

  • peptide-based vaccine
  • immunodominant epitope
  • immunoinformatics
  • immunogenic epitope
  • vaccination

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Published Papers (5 papers)

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Research

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24 pages, 4180 KiB  
Article
An In-Silico Investigation to Design a Multi-Epitopes Vaccine against Multi-Drug Resistant Hafnia alvei
by Fahad M. Alshabrmi, Faris Alrumaihi, Sahar Falah Alrasheedi, Wafa Abdullah I. Al-Megrin, Ahmad Almatroudi and Khaled S. Allemailem
Vaccines 2022, 10(7), 1127; https://doi.org/10.3390/vaccines10071127 - 15 Jul 2022
Cited by 5 | Viewed by 2785
Abstract
Antimicrobial resistance has become a significant health issue because of the misuse of antibiotics in our daily lives, resulting in high rates of morbidity and mortality. Hafnia alvei is a rod-shaped, Gram-negative and facultative anaerobic bacteria. The medical community has emphasized H. alvei [...] Read more.
Antimicrobial resistance has become a significant health issue because of the misuse of antibiotics in our daily lives, resulting in high rates of morbidity and mortality. Hafnia alvei is a rod-shaped, Gram-negative and facultative anaerobic bacteria. The medical community has emphasized H. alvei’s possible association with gastroenteritis. As of now, there is no licensed vaccine for H. alvei, and as such, computer aided vaccine design approaches could be an ideal approach to highlight the potential vaccine epitopes against this bacteria. By using bacterial pan-genome analysis (BPGA), we were able to study the entire proteomes of H. alvei with the aim of developing a vaccine. Based on the analysis, 20,370 proteins were identified as core proteins, which were further used in identifying potential vaccine targets based on several vaccine candidacy parameters. The prioritized vaccine targets against the bacteria are; type 1 fimbrial protein, flagellar hook length control protein (FliK), flagellar hook associated protein (FlgK), curli production assembly/transport protein (CsgF), fimbria/pilus outer membrane usher protein, fimbria/pilus outer membrane usher protein, molecular chaperone, flagellar filament capping protein (FliD), TonB-dependent hemoglobin /transferrin/lactoferrin family receptor, Porin (OmpA), flagellar basal body rod protein (FlgF) and flagellar hook-basal body complex protein (FliE). During the epitope prediction phase, different antigenic, immunogenic, non-Allergenic, and non-Toxic epitopes were predicted for the above-mentioned proteins. The selected epitopes were combined to generate a multi-epitope vaccine construct and a cholera toxin B subunit (adjuvant) was added to enhance the vaccine’s antigenicity. Downward analyses of vaccines were performed using a vaccine three-dimensional model. Docking studies have confirmed that the vaccine strongly binds with MHC-I, MHC-II, and TLR-4 immune cell receptors. Additionally, molecular dynamics simulations confirmed that the vaccine epitopes were exposed to nature and to the host immune system and interpreted strong intermolecular binding between the vaccine and receptors. Based on the results of the study, the model vaccine construct seems to have the capacity to produce protective immune responses in the host, making it an attractive candidate for further in vitro and in vivo studies. Full article
(This article belongs to the Special Issue Development of Epitope-Based Peptide Vaccine)
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19 pages, 4715 KiB  
Article
A New Epitope Selection Method: Application to Design a Multi-Valent Epitope Vaccine Targeting HRAS Oncogene in Squamous Cell Carcinoma
by Kush Savsani, Gabriel Jabbour and Sivanesan Dakshanamurthy
Vaccines 2022, 10(1), 63; https://doi.org/10.3390/vaccines10010063 - 31 Dec 2021
Cited by 6 | Viewed by 3520
Abstract
We developed an epitope selection method for the design of MHC targeting peptide vaccines. The method utilizes predictions for several clinical checkpoint filters, including binding affinity, immunogenicity, antigenicity, half-life, toxicity, IFNγ release, and instability. The accuracy of the prediction tools for these filter [...] Read more.
We developed an epitope selection method for the design of MHC targeting peptide vaccines. The method utilizes predictions for several clinical checkpoint filters, including binding affinity, immunogenicity, antigenicity, half-life, toxicity, IFNγ release, and instability. The accuracy of the prediction tools for these filter variables was confirmed using experimental data obtained from the Immune Epitope Database (IEDB). We also developed a graphical user interface computational tool called ‘PCOptim’ to assess the success of an epitope filtration method. To validate the filtration methods, we used a large data set of experimentally determined, immunogenic SARS-CoV-2 epitopes, which were obtained from a meta-analysis. The validation process proved that placing filters on individual parameters was the most effective method to select top epitopes. For a proof-of-concept, we designed epitope-based vaccine candidates for squamous cell carcinoma, selected from the top mutated epitopes of the HRAS gene. By comparing the filtered epitopes to PCOptim’s output, we assessed the success of the epitope selection method. The top 15 mutations in squamous cell carcinoma resulted in 16 CD8 epitopes which passed the clinical checkpoints filters. Notably, the identified HRAS epitopes are the same as the clinical immunogenic HRAS epitope-based vaccine candidates identified by the previous studies. This indicates further validation of our filtration method. We expect a similar turn-around for the other designed HRAS epitopes as a vaccine candidate for squamous cell carcinoma. Furthermore, we obtained a world population coverage of 89.45% for the top MHC Class I epitopes and 98.55% population coverage in the absence of the IFNγ release clinical checkpoint filter. We also identified some of the predicted human epitopes to be strong binders to murine MHC molecules, which provides insight into studying their immunogenicity in preclinical models. Further investigation in murine models could warrant the application of these epitopes for treatment or prevention of squamous cell carcinoma. Full article
(This article belongs to the Special Issue Development of Epitope-Based Peptide Vaccine)
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13 pages, 3404 KiB  
Article
In Silico Prediction of a Multitope Vaccine against Moraxella catarrhalis: Reverse Vaccinology and Immunoinformatics
by Mohamed A. Soltan, Nada Elbassiouny, Helmy Gamal, Eslam B. Elkaeed, Refaat A. Eid, Muhammad Alaa Eldeen and Ahmed A. Al-Karmalawy
Vaccines 2021, 9(6), 669; https://doi.org/10.3390/vaccines9060669 - 18 Jun 2021
Cited by 59 | Viewed by 6766
Abstract
Moraxella catarrhalis (M. catarrhalis) is a Gram-negative bacterium that can cause serious respiratory tract infections and middle ear infections in children and adults. M. catarrhalis has demonstrated an increasing rate of antibiotic resistance in the last few years, thus development of [...] Read more.
Moraxella catarrhalis (M. catarrhalis) is a Gram-negative bacterium that can cause serious respiratory tract infections and middle ear infections in children and adults. M. catarrhalis has demonstrated an increasing rate of antibiotic resistance in the last few years, thus development of an effective vaccine is a major health priority. We report here a novel designed multitope vaccine based on the mapped epitopes of the vaccine candidates filtered out of the whole proteome of M. catarrhalis. After analysis of 1615 proteins using a reverse vaccinology approach, only two proteins (outer membrane protein assembly factor BamA and LPS assembly protein LptD) were nominated as potential vaccine candidates. These proteins were found to be essential, outer membrane, virulent and non-human homologs with appropriate molecular weight and high antigenicity score. For each protein, cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL) and B cell lymphocyte (BCL) epitopes were predicted and confirmed to be highly antigenic and cover conserved regions of the proteins. The mapped epitopes constituted the base of the designed multitope vaccine where suitable linkers were added to conjugate them. Additionally, beta defensin adjuvant and pan-HLA DR-binding epitope (PADRE) peptide were also incorporated into the construct to improve the stimulated immune response. The constructed multitope vaccine was analyzed for its physicochemical, structural and immunological characteristics and it was found to be antigenic, soluble, stable, non-allergenic and have a high affinity to its target receptor. Although the in silico analysis of the current study revealed that the designed multitope vaccine has the ability to trigger a specific immune response against M. catarrhalis, additional translational research is required to confirm the effectiveness of the designed vaccine. Full article
(This article belongs to the Special Issue Development of Epitope-Based Peptide Vaccine)
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19 pages, 4355 KiB  
Article
Use of a Novel Peptide Welding Technology Platform for the Development of B- and T-Cell Epitope-Based Vaccines
by Francesco Nicoli, Salvatore Pacifico, Eleonora Gallerani, Erika Marzola, Valentina Albanese, Valentina Finessi, Sian Llewellyn-Lacey, David A. Price, Victor Appay, Peggy Marconi, Remo Guerrini, Antonella Caputo and Riccardo Gavioli
Vaccines 2021, 9(5), 526; https://doi.org/10.3390/vaccines9050526 - 19 May 2021
Cited by 1 | Viewed by 2747
Abstract
Peptide vaccines incorporating B- and T-cell epitopes have shown promise in the context of various cancers and infections. These vaccines are relatively simple to manufacture, but more immunogenic formulations are considered a priority. We developed tetrabranched derivatives for this purpose based on a [...] Read more.
Peptide vaccines incorporating B- and T-cell epitopes have shown promise in the context of various cancers and infections. These vaccines are relatively simple to manufacture, but more immunogenic formulations are considered a priority. We developed tetrabranched derivatives for this purpose based on a novel peptide welding technology (PWT). PWTs provide molecular scaffolds for the efficient synthesis of ultrapure peptide dendrimers, which allow the delivery of multiple ligands within a single macromolecular structure. Peptide vaccines incorporating T-cell epitopes derived from melanoma and B-cell epitopes derived from human immunodeficiency virus, synthesized using this approach, elicited primary immune responses in vitro and in vivo. Subcutaneous administration of the B-cell epitope-based vaccines also elicited more potent humoral responses than subcutaneous administration of the corresponding peptides alone. Highly immunogenic peptide epitope-based vaccines can therefore be generated quickly and easily using a novel PWT. Full article
(This article belongs to the Special Issue Development of Epitope-Based Peptide Vaccine)
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Review

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21 pages, 2520 KiB  
Review
Peptide-Based Vaccines: Foot-and-Mouth Disease Virus, a Paradigm in Animal Health
by Mar Forner, Rodrigo Cañas-Arranz, Sira Defaus, Patricia de León, Miguel Rodríguez-Pulido, Llilianne Ganges, Esther Blanco, Francisco Sobrino and David Andreu
Vaccines 2021, 9(5), 477; https://doi.org/10.3390/vaccines9050477 - 8 May 2021
Cited by 15 | Viewed by 5794
Abstract
Vaccines are considered one of the greatest global health achievements, improving the welfare of society by saving lives and substantially reducing the burden of infectious diseases. However, few vaccines are fully effective, for reasons ranging from intrinsic limitations to more contingent shortcomings related, [...] Read more.
Vaccines are considered one of the greatest global health achievements, improving the welfare of society by saving lives and substantially reducing the burden of infectious diseases. However, few vaccines are fully effective, for reasons ranging from intrinsic limitations to more contingent shortcomings related, e.g., to cold chain transport, handling and storage. In this context, subunit vaccines where the essential antigenic traits (but not the entire pathogen) are presented in rationally designed fashion have emerged as an attractive alternative to conventional ones. In particular, this includes the option of fully synthetic peptide vaccines able to mimic well-defined B- and T-cell epitopes from the infectious agent and to induce protection against it. Although, in general, linear peptides have been associated to low immunogenicity and partial protection, there are several strategies to address such issues. In this review, we report the progress towards the development of peptide-based vaccines against foot-and-mouth disease (FMD) a highly transmissible, economically devastating animal disease. Starting from preliminary experiments using single linear B-cell epitopes, recent research has led to more complex and successful second-generation vaccines featuring peptide dendrimers containing multiple copies of B- and T-cell epitopes against FMD virus or classical swine fever virus (CSFV). The usefulness of this strategy to prevent other animal and human diseases is discussed. Full article
(This article belongs to the Special Issue Development of Epitope-Based Peptide Vaccine)
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