Genomic Medicine and Advances in Vaccine Technology and Development 2.0

A special issue of Vaccines (ISSN 2076-393X). This special issue belongs to the section "Cellular/Molecular Immunology".

Deadline for manuscript submissions: closed (28 February 2022) | Viewed by 34096

Special Issue Editors


E-Mail Website
Guest Editor
Department of Translational Medicine and Surgery, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
Interests: inflammation; sepsis; microbiota; immunology
Special Issues, Collections and Topics in MDPI journals

E-Mail Website
Guest Editor
Emergency Medicine Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
Interests: immunology; vaccination; microbiota; emergency medicine
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The importance of vaccines is constantly growing both in importance and economic value.  The development process for vaccine development from research to marketing may take 10 years and cost approx 1 billion dollars but the success rate of vaccine development may be very low. Critical interest in research to maintain vaccines that enhance the immune response to prevent diseases has been the focus of vaccine development. WHO funded vaccine preventable conditions and disease projects may only be successful with effective low calorie nutrigenomic diets that activate anti-aging gene expression critical to maintain the primary and secondary immune response in man and other species. In the developing world increasing therapeutic anti-aging protein levels in the plasma and cells has become important to maintain the immune system with relevance to vaccine technology. Biotherapy, core body temperature and anti-aging gene activation with relevance to the chronic disease epidemic is critical to prevent mitophagy and autoimmune disease linked to the prevention of inactivation of vaccines and vaccine development. Articles for this special issue are required to assess the role of anti-aging genes and activation of the transcriptional co-activator relevant to the adaptive immune response that determines the success of old and new vaccine development.

Dr. Rossella Cianci
Dr. Laura Franza
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Vaccines is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Genomic medicine
  • vaccine development
  • diet
  • anti-aging genes
  • transcriptional regulator
  • autoimmune disease
  • developing world
  • immune response
  • anti-aging protein
  • biotherapy
  • species

Published Papers (11 papers)

Order results
Result details
Select all
Export citation of selected articles as:

Editorial

Jump to: Research

3 pages, 182 KiB  
Editorial
Recent Advances in Vaccine Technology and Design
by Rossella Cianci and Laura Franza
Vaccines 2022, 10(4), 624; https://doi.org/10.3390/vaccines10040624 - 15 Apr 2022
Cited by 2 | Viewed by 1444
Abstract
If up until three years ago, infectious diseases were a lesser concern when compared to non-communicable diseases in Western countries, the ongoing pandemic has reminded us that things are not so clean-cut [...] Full article

Research

Jump to: Editorial

15 pages, 30278 KiB  
Article
Whole Proteome-Based Therapeutic Targets Annotation and Designing of Multi-Epitope-Based Vaccines against the Gram-Negative XDR-Alcaligenes faecalis Bacterium
by Metab Alharbi, Abdulrahman Alshammari, Abdullah F. Alasmari, Saud Alharbi, Muhammad Tahir ul Qamar, Sumra Wajid Abbasi, Bilal Shaker and Sajjad Ahmad
Vaccines 2022, 10(3), 462; https://doi.org/10.3390/vaccines10030462 - 17 Mar 2022
Cited by 12 | Viewed by 2279
Abstract
This study involved therapeutic targets mining for the extremely drug-resistant bacterial species called Alcaligenes faecalis, which is known to infect humans. The infections caused by this species in different parts of the human body have been linked with a higher degree of [...] Read more.
This study involved therapeutic targets mining for the extremely drug-resistant bacterial species called Alcaligenes faecalis, which is known to infect humans. The infections caused by this species in different parts of the human body have been linked with a higher degree of resistance to several classes of antibiotics. Meanwhile, alternate therapeutic options are needed to treat these bacterial infections in clinical settings. In the current study, a subtractive proteomics approach was adapted to annotate the whole proteome of Alcaligenes faecalis and prioritize target proteins for vaccine-related therapeutics design. This was followed by targeted protein-specific immune epitope prediction and prioritization. The shortlisted epitopes were further subjected to structural design and in silico validation of putative vaccines against Alcaligenes faecalis. The final vaccine designs were also evaluated for potential interaction analysis with human TLR-2 through molecular docking. Finally, the putative vaccines were subjected to in silico cloning and immune simulation approaches to ensure the feasibility of the target-specific vaccine constructs in further experimental designs. Full article
Show Figures

Figure 1

25 pages, 9356 KiB  
Article
Design of a Multi-Epitopes Vaccine against Hantaviruses: An Immunoinformatics and Molecular Modelling Approach
by Saba Ismail, Sumra Wajid Abbasi, Maha Yousaf, Sajjad Ahmad, Khalid Muhammad and Yasir Waheed
Vaccines 2022, 10(3), 378; https://doi.org/10.3390/vaccines10030378 - 28 Feb 2022
Cited by 15 | Viewed by 3269
Abstract
Hantaviruses are negative-sense, enveloped, single-stranded RNA viruses of the family Hantaviridae. In recent years, rodent-borne hantaviruses have emerged as novel zoonotic viruses posing a substantial health issue and socioeconomic burden. In the current research, a reverse vaccinology approach was applied to design a [...] Read more.
Hantaviruses are negative-sense, enveloped, single-stranded RNA viruses of the family Hantaviridae. In recent years, rodent-borne hantaviruses have emerged as novel zoonotic viruses posing a substantial health issue and socioeconomic burden. In the current research, a reverse vaccinology approach was applied to design a multi-epitope-based vaccine against hantavirus. A set of 340 experimentally reported epitopes were retrieved from Virus Pathogen Database and Analysis Resource (ViPR) and subjected to different analyses such as antigenicity, allergenicity, solubility, IFN gamma, toxicity, and virulent checks. Finally, 10 epitopes which cleared all the filters used were linked with each other through specific GPGPG linkers to construct a multi-antigenic epitope vaccine. The designed vaccine was then joined to three different adjuvants—TLR4-agonist adjuvant, β-defensin, and 50S ribosomal protein L7/L12—using an EAAAK linker to boost up immune-stimulating responses and check the potency of vaccine with each adjuvant. The designed vaccine structures were modelled and subjected to error refinement and disulphide engineering to enhance their stability. To understand the vaccine binding affinity with immune cell receptors, molecular docking was performed between the designed vaccines and TLR4; the docked complex with a low level of global energy was then subjected to molecular dynamics simulations to validate the docking results and dynamic behaviour. The docking binding energy of vaccines with TLR4 is −29.63 kcal/mol (TLR4-agonist), −3.41 kcal/mol (β-defensin), and −11.03 kcal/mol (50S ribosomal protein L7/L12). The systems dynamics revealed all three systems to be highly stable with a root-mean-square deviation (RMSD) value within 3 Å. To test docking predictions and determine dominant interaction energies, binding free energies of vaccine(s)–TLR4 complexes were calculated. The net binding energy of the systems was as follows: TLR4-agonist vaccine with TLR4 (MM–GBSA, −1628.47 kcal/mol and MM–PBSA, −37.75 kcal/mol); 50S ribosomal protein L7/L12 vaccine with TLR4 complex (MM–GBSA, −194.62 kcal/mol and MM–PBSA, −150.67 kcal/mol); β-defensin vaccine with TLR4 complex (MM–GBSA, −9.80 kcal/mol and MM–PBSA, −42.34 kcal/mol). Finally, these findings may aid experimental vaccinologists in developing a very potent hantavirus vaccine. Full article
Show Figures

Figure 1

25 pages, 5426 KiB  
Article
Designing a Recombinant Vaccine against Providencia rettgeri Using Immunoinformatics Approach
by Saba Gul, Sajjad Ahmad, Asad Ullah, Saba Ismail, Muhammad Khurram, Muhammad Tahir ul Qamar, Abdulrahim R. Hakami, Ali G. Alkhathami, Faris Alrumaihi and Khaled S. Allemailem
Vaccines 2022, 10(2), 189; https://doi.org/10.3390/vaccines10020189 - 25 Jan 2022
Cited by 34 | Viewed by 4077
Abstract
Antibiotic resistance (AR) is the resistance mechanism pattern in bacteria that evolves over some time, thus protecting the bacteria against antibiotics. AR is due to bacterial evolution to make itself fit to changing environmental conditions in a quest for survival of the fittest. [...] Read more.
Antibiotic resistance (AR) is the resistance mechanism pattern in bacteria that evolves over some time, thus protecting the bacteria against antibiotics. AR is due to bacterial evolution to make itself fit to changing environmental conditions in a quest for survival of the fittest. AR has emerged due to the misuse and overuse of antimicrobial drugs, and few antibiotics are now left to deal with these superbug infections. To combat AR, vaccination is an effective method, used either therapeutically or prophylactically. In the current study, an in silico approach was applied for the design of multi-epitope-based vaccines against Providencia rettgeri, a major cause of traveler’s diarrhea. A total of six proteins: fimbrial protein, flagellar hook protein (FlgE), flagellar basal body L-ring protein (FlgH), flagellar hook-basal body complex protein (FliE), flagellar basal body P-ring formation protein (FlgA), and Gram-negative pili assembly chaperone domain proteins, were considered as vaccine targets and were utilized for B- and T-cell epitope prediction. The predicted epitopes were assessed for allergenicity, antigenicity, virulence, toxicity, and solubility. Moreover, filtered epitopes were utilized in multi-epitope vaccine construction. The predicted epitopes were joined with each other through specific GPGPG linkers and were joined with cholera toxin B subunit adjuvant via another EAAAK linker in order to enhance the efficacy of the designed vaccine. Docking studies of the designed vaccine construct were performed with MHC-I (PDB ID: 1I1Y), MHC-II (1KG0), and TLR-4 (4G8A). Findings of the docking study were validated through molecular dynamic simulations, which confirmed that the designed vaccine showed strong interactions with the immune receptors, and that the epitopes were exposed to the host immune system for proper recognition and processing. Additionally, binding free energies were estimated, which highlighted both electrostatic energy and van der Waals forces to make the complexes stable. Briefly, findings of the current study are promising and may help experimental vaccinologists to formulate a novel multi-epitope vaccine against P. rettgeri. Full article
Show Figures

Figure 1

19 pages, 9382 KiB  
Article
Development of a Candidate Multi-Epitope Subunit Vaccine against Klebsiella aerogenes: Subtractive Proteomics and Immuno-Informatics Approach
by Ahitsham Umar, Asma Haque, Youssef Saeed Alghamdi, Mutaib M Mashraqi, Abdur Rehman, Farah Shahid, Mohsin Khurshid and Usman Ali Ashfaq
Vaccines 2021, 9(11), 1373; https://doi.org/10.3390/vaccines9111373 - 22 Nov 2021
Cited by 10 | Viewed by 3450
Abstract
Klebsiella aerogenes is a Gram-negative bacterium which has gained considerable importance in recent years. It is involved in 10% of nosocomial and community-acquired urinary tract infections and 12% of hospital-acquired pneumonia. This organism has an intrinsic ability to produce inducible chromosomal AmpC beta-lactamases, [...] Read more.
Klebsiella aerogenes is a Gram-negative bacterium which has gained considerable importance in recent years. It is involved in 10% of nosocomial and community-acquired urinary tract infections and 12% of hospital-acquired pneumonia. This organism has an intrinsic ability to produce inducible chromosomal AmpC beta-lactamases, which confer high resistance. The drug resistance in K. aerogenes has been reported in China, Israel, Poland, Italy and the United States, with a high mortality rate (~50%). This study aims to combine immunological approaches with molecular docking approaches for three highly antigenic proteins to design vaccines against K. aerogenes. The synthesis of the B-cell, T-cell (CTL and HTL) and IFN-γ epitopes of the targeted proteins was performed and most conserved epitopes were chosen for future research studies. The vaccine was predicted by connecting the respective epitopes, i.e., B cells, CTL and HTL with KK, AAY and GPGPG linkers and all these were connected with N-terminal adjuvants with EAAAK linker. The humoral response of the constructed vaccine was measured through IFN-γ and B-cell epitopes. Before being used as vaccine candidate, all identified B-cell, HTL and CTL epitopes were tested for antigenicity, allergenicity and toxicity to check the safety profiles of our vaccine. To find out the compatibility of constructed vaccine with receptors, MHC-I, followed by MHC-II and TLR4 receptors, was docked with the vaccine. Lastly, in order to precisely certify the proper expression and integrity of our construct, in silico cloning was carried out. Further studies are needed to confirm the safety features and immunogenicity of the vaccine. Full article
Show Figures

Figure 1

18 pages, 4905 KiB  
Article
Immunoinformatics and Immunogenetics-Based Design of Immunogenic Peptides Vaccine against the Emerging Tick-Borne Encephalitis Virus (TBEV) and Its Validation through In Silico Cloning and Immune Simulation
by Muhammad Suleman, Muhammad Tahir ul Qamar, Kiran, Samreen Rasool, Aneela Rasool, Aqel Albutti, Noorah Alsowayeh, Ameen S. S. Alwashmi, Mohammad Abdullah Aljasir, Sajjad Ahmad, Zahid Hussain, Muhammad Rizwan, Syed Shujait Ali, Abbas Khan and Dong-Qing Wei
Vaccines 2021, 9(11), 1210; https://doi.org/10.3390/vaccines9111210 - 20 Oct 2021
Cited by 12 | Viewed by 2910
Abstract
Pegivirus, HPgV, earlier known as Gb virus and hepatitis G virus, is an enveloped, positive-stranded RNA and lymphotropic virus classified into the Flaviviridae family. The transmission routes primarily involve blood products, with infections worldwide, leading up to 25% of persistent infections. To date, [...] Read more.
Pegivirus, HPgV, earlier known as Gb virus and hepatitis G virus, is an enveloped, positive-stranded RNA and lymphotropic virus classified into the Flaviviridae family. The transmission routes primarily involve blood products, with infections worldwide, leading up to 25% of persistent infections. To date, no effective therapeutic means are available to resolve Pegivirus infections. Effective vaccine therapeutics are the best alternative to manage this disease and any associated potential pandemic. Thus, whole proteome-based mining of immunogenic peptides, i.e., CTL (cytotoxic T lymphocytes), HTL (helper T lymphocytes) and B cell epitopes were mapped to design a vaccine ensemble. Our investigation revealed that 29 different epitopes impart a critical role in immune response induction, which was also validated by exploring its physiochemical properties and experimental feasibility. In silico expression and host immune simulation using an agent-based modeling approach confirmed the induction of both primary and secondary immune factors such as IL, cytokines and antibodies. The current study warrants further lab experiments to demonstrate its efficacy and safety. Full article
Show Figures

Figure 1

14 pages, 2909 KiB  
Article
Associations between Allelic Variants of the Human IgH 3′ Regulatory Region 1 and the Immune Response to BNT162b2 mRNA Vaccine
by Mattia Colucci, Elisabetta De Santis, Beatrice Totti, Mattia Miroballo, Francesco Tamiro, Giovanni Rossi, Ada Piepoli, Gabriella De Vincentis, Antonio Greco, Alessandra Mangia, Rossella Cianci, Lazzaro Di Mauro, Giuseppe Miscio and Vincenzo Giambra
Vaccines 2021, 9(10), 1207; https://doi.org/10.3390/vaccines9101207 - 19 Oct 2021
Cited by 8 | Viewed by 2478
Abstract
The escalation of Coronavirus disease 2019 (COVID-19) has required the development of safe and effective vaccines against the severe acute respiratory syndrome coronavirus 2-associated (SARS-CoV-2), which is the causative agent of the disease. Here, we determined the levels of antibodies, antigen-specific B cells, [...] Read more.
The escalation of Coronavirus disease 2019 (COVID-19) has required the development of safe and effective vaccines against the severe acute respiratory syndrome coronavirus 2-associated (SARS-CoV-2), which is the causative agent of the disease. Here, we determined the levels of antibodies, antigen-specific B cells, against a recombinant GFP-tagged SARS-CoV-2 spike (S) protein and total T and NK cell subsets in subjects up to 20 days after the injection of the BNT162b2 (Pfizer–BioNTech) vaccine using a combined approach of serological and flow cytometry analyses. In former COVID-19 patients and highly responsive individuals, a significant increase of antibody production was detected, simultaneous with an expansion of antigen-specific B cell response and the total number of NK-T cells. Additionally, through a genetic screening of a specific polymorphic region internal to the 3’ regulatory region 1 (3’RR1) of human immunoglobulin constant-gene (IgH) locus, we identified different single-nucleotide polymorphic (SNP) variants associated with either highly or lowly responsive subjects. Taken together, these results suggest that favorable genetic backgrounds and immune profiles support the progression of an effective response to BNT162b2 vaccination. Full article
Show Figures

Figure 1

23 pages, 4569 KiB  
Article
A Comprehensive Computer Aided Vaccine Design Approach to Propose a Multi-Epitopes Subunit Vaccine against Genus Klebsiella Using Pan-Genomics, Reverse Vaccinology, and Biophysical Techniques
by Khaled S. Allemailem
Vaccines 2021, 9(10), 1087; https://doi.org/10.3390/vaccines9101087 - 27 Sep 2021
Cited by 13 | Viewed by 2989
Abstract
Klebsiella is a genus of nosocomial bacterial pathogens and is placed in the most critical list of World Health Organization (WHO) for development of novel therapeutics. The pathogens of the genus are associated with high mortality and morbidity. Owing to their strong resistance [...] Read more.
Klebsiella is a genus of nosocomial bacterial pathogens and is placed in the most critical list of World Health Organization (WHO) for development of novel therapeutics. The pathogens of the genus are associated with high mortality and morbidity. Owing to their strong resistance profile against different classes of antibiotics and nonavailability of a licensed vaccine, urgent efforts are required to develop a novel vaccine candidate that can tackle all pathogenic species of the Klebsiella genus. The present study aims to design a broad-spectrum vaccine against all species of the Klebsiella genus with objectives to identify the core proteome of pathogen species, prioritize potential core vaccine proteins, analyze immunoinformatics of the vaccine proteins, construct a multi-epitopes vaccine, and provide its biophysical analysis. Herein, we investigated all reference species of the genus to reveal their core proteome. The core proteins were then subjected to multiple reverse vaccinology checks that are mandatory for the prioritization of potential vaccine candidates. Two proteins (TonB-dependent siderophore receptor and siderophore enterobactin receptor FepA) were found to fulfill all vaccine parameters. Both these proteins harbor several potent B-cell-derived T-cell epitopes that are antigenic, nonallergic, nontoxic, virulent, water soluble, IFN-γ producer, and efficient binder of DRB*0101 allele. The selected epitopes were modeled into a multi-epitope peptide comprising linkers and Cholera Toxin B adjuvant. For docking with innate immune and MHC receptors and afterward molecular dynamics simulations and binding free energy analysis, the vaccine structure was modeled for tertiary structure and refined for structural errors. To assess the binding affinity and presentation of the designed vaccine construct, binding mode and interactions analysis were performed using molecular docking and molecular dynamics simulation techniques. These biophysical approaches illustrated the vaccine as a good binder to the immune receptors and revealed robust interactions energies. The vaccine sequence was further translated to nucleotide sequence and cloned into an appropriate vector for expressing it at high rate in Escherichia coli K12 strain. In addition, the vaccine was illustrated to generate a good level of primary, secondary, and tertiary immune responses, proving good immunogenicity of the vaccine. Based on the reported results, the vaccine can be a good candidate to be evaluated for effectiveness in wet laboratory validation studies. Full article
Show Figures

Figure 1

22 pages, 3361 KiB  
Article
Proteome-Wide Mapping and Reverse Vaccinology Approaches to Design a Multi-Epitope Vaccine against Clostridium perfringens
by Fahad M. Aldakheel, Amna Abrar, Samman Munir, Sehar Aslam, Khaled S. Allemailem, Mohsin Khurshid and Usman Ali Ashfaq
Vaccines 2021, 9(10), 1079; https://doi.org/10.3390/vaccines9101079 - 26 Sep 2021
Cited by 14 | Viewed by 3204
Abstract
C. perfringens is a highly versatile bacteria of livestock and humans, causing enteritis (a common food-borne illness in humans), enterotoxaemia (in which toxins are formed in the intestine which damage and destroy organs, i.e., the brain), and gangrene (wound infection). There is no [...] Read more.
C. perfringens is a highly versatile bacteria of livestock and humans, causing enteritis (a common food-borne illness in humans), enterotoxaemia (in which toxins are formed in the intestine which damage and destroy organs, i.e., the brain), and gangrene (wound infection). There is no particular cure for the toxins of C. perfringens. Supportive care (medical control of pain, intravenous fluids) is the standard treatment. Therefore, a multiple-epitope vaccine (MEV) should be designed to battle against C. perfringens infection. Furthermore, the main objective of this in silico investigation is to design an MEV that targets C. perfringens. For this purpose, we selected the top three proteins that were highly antigenic using immuno-informatics approaches, including molecular docking. B-cells, IFN-gamma, and T cells for target proteins were predicted and the most conserved epitopes were selected for further investigation. For the development of the final MEV, epitopes of LBL5, CTL17, and HTL13 were linked to GPGPG, AAY, and KK linkers. The vaccine N-end was joined to an adjuvant through an EAAK linker to improve immunogenicity. After the attachment of linkers and adjuvants, the final construct was 415 amino acids. B-cell and IFN-gamma epitopes demonstrate that the model structure is enhanced for humoral and cellular immune responses. To validate the immunogenicity and safety of the final construct, various physicochemical properties, and other properties such as antigenicity and non-allergens, were evaluated. Furthermore, molecular docking was carried out for verification of vaccine compatibility with the receptor, evaluated in silico. Also, in silico cloning was employed for the verification of the proper expression and credibility of the construct. Full article
Show Figures

Figure 1

12 pages, 1143 KiB  
Article
Development of a Quantitative One-Step RT-PCR Method for the Detection of Sabin 2 Virus Contamination in a Novel Oral Poliovirus Vaccine Type 2
by Hasmik Manukyan, Erman Tritama, Rahnuma Wahid, Azeem Ansari, John Konz, Konstantin Chumakov and Majid Laassri
Vaccines 2021, 9(7), 688; https://doi.org/10.3390/vaccines9070688 - 23 Jun 2021
Cited by 1 | Viewed by 2551
Abstract
To control circulating vaccine-derived type 2 poliovirus outbreaks, a more genetically stable novel Oral Poliovirus Vaccine type 2 (nOPV2) was developed by targeted modifications of Sabin 2 genome. Since the use of OPV2 made of Sabin 2 strain has been stopped, it is [...] Read more.
To control circulating vaccine-derived type 2 poliovirus outbreaks, a more genetically stable novel Oral Poliovirus Vaccine type 2 (nOPV2) was developed by targeted modifications of Sabin 2 genome. Since the use of OPV2 made of Sabin 2 strain has been stopped, it is important to exclude the possibility that batches of nOPV2 are contaminated with Sabin 2 virus. Here, we report the development of a simple quantitative one-step reverse-transcription polymerase chain reaction assay for the detection and quantitation of Sabin 2 virus in the presence of overwhelming amounts of nOPV2 strain. The method is specific and linear within 8 log10 range even in the presence of relevant amounts of nOPV2 virus. It is sensitive, with a lower limit of detection of 0.2 CCID50/mL (an equivalent of 198 genome copies per mL), and generates reproducible results. This assay can be used for quality control and lot release of the nOPV2. Full article
Show Figures

Figure 1

21 pages, 26247 KiB  
Article
Integrated Core Proteomics, Subtractive Proteomics, and Immunoinformatics Investigation to Unveil a Potential Multi-Epitope Vaccine against Schistosomiasis
by Abdur Rehman, Sajjad Ahmad, Farah Shahid, Aqel Albutti, Ameen S. S. Alwashmi, Mohammad Abdullah Aljasir, Naif Alhumeed, Muhammad Qasim, Usman Ali Ashfaq and Muhammad Tahir ul Qamar
Vaccines 2021, 9(6), 658; https://doi.org/10.3390/vaccines9060658 - 16 Jun 2021
Cited by 31 | Viewed by 4524
Abstract
Schistosomiasis is a parasitic infection that causes considerable morbidity and mortality in the world. Infections of parasitic blood flukes, known as schistosomes, cause the disease. No vaccine is available yet and thus there is a need to design an effective vaccine against schistosomiasis. [...] Read more.
Schistosomiasis is a parasitic infection that causes considerable morbidity and mortality in the world. Infections of parasitic blood flukes, known as schistosomes, cause the disease. No vaccine is available yet and thus there is a need to design an effective vaccine against schistosomiasis. Schistosoma japonicum, Schistosoma mansoni, and Schistosoma haematobium are the main pathogenic species that infect humans. In this research, core proteomics was combined with a subtractive proteomics pipeline to identify suitable antigenic proteins for the construction of a multi-epitope vaccine (MEV) against human-infecting Schistosoma species. The pipeline revealed two antigenic proteins—calcium binding and mycosubtilin synthase subunit C—as promising vaccine targets. T and B cell epitopes from the targeted proteins were predicted using multiple bioinformatics and immunoinformatics databases. Seven cytotoxic T cell lymphocytes (CTL), three helper T cell lymphocytes (HTL), and four linear B cell lymphocytes (LBL) epitopes were fused with a suitable adjuvant and linkers to design a 217 amino-acid-long MEV. The vaccine was coupled with a TLR-4 agonist (RS-09; Sequence: APPHALS) adjuvant to enhance the immune responses. The designed MEV was stable, highly antigenic, and non-allergenic to human use. Molecular docking, molecular dynamics (MD) simulations, and molecular mechanics/generalized Born surface area (MMGBSA) analysis were performed to study the binding affinity and molecular interactions of the MEV with human immune receptors (TLR2 and TLR4) and MHC molecules (MHC I and MHC II). The MEV expression capability was tested in an Escherichia coli (strain-K12) plasmid vector pET-28a(+). Findings of these computer assays proved the MEV as highly promising in establishing protective immunity against the pathogens; nevertheless, additional validation by in vivo and in vitro experiments is required to discuss its real immune-protective efficacy. Full article
Show Figures

Figure 1

Back to TopTop