Efficient Multi-epitope Vaccine Research Articles

A multi-epitope vaccine designed against blood-stage of malaria: an immunoinformatic and structural approach

Malaria is a complex disease caused by parasites of the genus Plasmodium and is the leading cause of morbidity and mortality worldwide. The most severe form of malaria disease is caused by Plasmodium falciparum. Thus, a combination of different approaches is needed to control malaria. Resistance to first-line drugs and insecticides, on the other hand, makes the need for an effective vaccination more urgent than ever. Because erythrocyte parasites cause the most clinical symptoms, developing a vaccination for this stage of infection might be highly beneficial. In this research, we employed various bioinformatics methods to create an efficient multi-epitope vaccine that induces antibodies against the blood stage of malaria infection. For this purpose, we selected the malaria PfGARP protein as the target here. The B, HTL epitopes, and epitope conservation were predicted. The predicted epitopes (including 5 B and 5 HTL epitopes) were connected using suitable linkers, and the flagellin molecule was used as an adjuvant to improve its immunogenicity. The final construct vaccine with 414 amino acids long was designed. The vaccine's allergenicity, antigenicity, solubility, physicochemical characteristics, 2D and 3D structure modeling, molecular docking, molecular dynamics simulation, in silico cloning, and immunological simulation were tested. In silico immune simulation results showed significantly elevated IgG1 and IgM and T helper cells, INF γ, IL 2, and B-cell populations after the injection of the designed vaccine. These significant computational analyses indicated that our proposed vaccine candidate might activate suitable immune responses against malaria. However, in vitro and in vivo studies are essential for further validation.

Development of a Novel Multi-Epitope Vaccine Candidate against Streptococcus Iniae Infection in Fish: An Immunoinformatics Study.

Streptococcus Iniae infection is recognized as a disease with substantial economic losses, infecting a wide range of fish species. The limitations of current vaccines and strategies have led to the identification of new methods to control this disease. Multi-epitope vaccines which employ various immunogenic proteins can be promising. The current research project aimed to design an efficient multi-epitope vaccine against Streptococcus Iniae infection in fish. To this end, six immunogenic proteins of Streptococcus Iniae, including FBA, ENO, Sip11, GAPDH, MtsB, and SCPI proteins, were applied for epitope prediction. The best B cell, T cell, and IFNγ epitopes of the immunogenic proteins, as well as interleukin-8, were used to construct a multi-epitope vaccine. Thereafter, different parameters of the designed vaccine, including physicochemical features, antigenicity, secondary structure, and tertiary structure, were evaluated. Moreover, the interaction of the interleukin-8 domain of the designed vaccine and its receptor was investigated by molecular docking strategy. Finally, nucleotide sequence of the vaccine was adapted to express in Escherichia coli. The results of the present study pointed out that the designed vaccine was a stable vaccine with molecular weight and antigenicity score of 45 kDa and 0.936, respectively. Furthermore, the structure analysis results revealed that the designed vaccine contained 23.49% alpha helix, with 90.5% residues in favored region. Finally, it was demonstrated that the interleukin-8 domain of the designed vaccine could be successfully docked to its receptor with the lowest energy of -1020.9. Based on the obtained results, it seems that the designed vaccine can be an efficient candidate to prevent Streptococcus Iniae infection in fish.

Computational design of a new multi-epitope vaccine using immunoinformatics approach against mastitis disease

Mastitis disease causes significant economic losses in dairy farms by reducing milk production, increasing production costs, and reducing milk quality. Streptococcus agalactiae continues to be a major cause of mastitis in dairy cattle. To date, there has been no approved multi-epitope vaccine against this pathogen in the market. In the present study, an efficient multi-epitope vaccine against S. agalactiae, the causative agent of mastitis, was designed using various immonoinformtics approaches. Potential epitopes were selected from Sip protein to improve vaccine immunogenicity. The designed vaccine is more antigenic in nature. Then, linkers and profilin adjuvant were added to enhance the immunity of vaccines. The designed vaccine was evaluated in terms of molecular weight, PI, immunogenicity, Toxicity, and allergenicity. Prediction of three-dimensional (3 D) structure of multi-epitope vaccine, followed by refinement and validation, was conducted to obtain a high-quality 3 D structure of the designed multi-epitope vaccine. The designed vaccine was then subjected to molecular docking with Toll-like receptor 11 (TLR11) receptor to evaluate its binding efficiency followed by dynamic simulation for stable interaction. In silico cloning approach was carried out to improve the expression of the vaccine construct. These analyses indicate that the designed multi-epitope vaccine may produce particular immune responses against S. agalactiae and may be further helpful to control mastitis after in vitro and in vivo immunological assays.

Designing an efficient multi-epitope vaccine displaying interactions with diverse HLA molecules for an efficient humoral and cellular immune response to prevent COVID-19 infection

ABSTRACT Background The novel SARS-CoV-2 coronavirus, the causative agent of the ongoing pandemic COVID-19 disease continues to infect people globally and has infected millions of humans worldwide. However, no effective vaccine against this virus exists. Method Using Immunoinformatics, epitopic sequences from multiple glycoproteins that play crucial role in pathogenesis were identified. Particularly, epitopes were mapped from conserved receptor-binding domain of spike protein which have been experimentally validated in SARS-CoV-1 as a promising target for vaccine development. Results A multi-epitopic vaccine construct comprising of B-cell, CTL, HTL epitopes was developed along with fusion of adjuvant and linkers. The epitopes identified herein are reported for the first time and were predicted to be highly antigenic, stable, nonallergen, nontoxic and displayed conservation across several SARS-CoV-2 isolates from different countries. Additionally, the epitopes associated with maximum HLA alleles and population coverage analysis shows the proposed epitopes would be a relevant representative of large proportion of the world population. A reliable three-dimensional structure of the vaccine construct was developed. Consequently, docking and molecular-dynamics simulation ensured the stable interaction between vaccine and innate-immune receptor.

Designing an efficient multi-epitope vaccine against Campylobacter jejuni using immunoinformatics and reverse vaccinology approach

Campylobacterjejuni causes acute diarrhea as a leading cause of morbidity and mortality in children especially in the developing countries of Asia and Africa. C.jejuni has been identified as a member of the priority pathogens category due to the sudden emergence of multidrug-resistant isolates. Therefore, it is important to develop a protective vaccine against this pathogen. In the present study, the Reverse vaccinology approach was used to identify vaccine targets from the proteome of diarrheagenic C. jejuni strain NCTC11168 for the development of chimeric vaccine candidates against C. jejuni. Pathogen proteins that have adhesin like properties and role in virulence but not present in the human host were selected for the design of a multi-epitope vaccine. MHC class I & II and B-cell epitopes present in the selected vaccine target proteins were screened using different immunoinformatics tools. The commonly predicted epitopes from their corresponding different servers were selected and further shortlisted based on their immunogenicity, antigenicity, and toxicity analysis. Shortlisted peptides were joined by GPGPG linkers to design a multi-epitope vaccine construct. Immune-modulating adjuvant monophosphoryl lipid sequence was added with the vaccine construct's N terminal using EAAAK linkers to enhance the immunogenicity. The designed vaccine construct was evaluated by antigenicity, allergenicity, solubility, and physicochemical analysis using various bioinformatics tools. A three-dimensional model of vaccine construct was modeled by the Phyre2 server and refinement by the GalaxyRefine tool. Constructed model quality was validated by the ProSA-web error-detection tool and the Ramachandran plot. After that vaccine model was docked with TLR-4 protein and complex stability confirmed by molecular dynamics simulation studies. Finally, In-silico cloning of vaccine constructs into a vector was performed to ensuring its effective expression in the microbial system.

Immunoinformatics-aided design of a potential multi-epitope peptide vaccine against Leishmania infantum

Visceral leishmaniasis (VL) or kala-azar, the most severe form of the disease, is endemic in more than eighty countries across the world. To date, there is no approved vaccine against VL in the market. Recent advances in reverse vaccinology could be promising approach in designing the efficient vaccine for VL treatment. In this study, an efficient multi-epitope vaccine against Leishmania infantum, the causative agent of VL, was designed using various computational vaccinology methods. Potential immunodominant epitopes were selected from four antigenic proteins, including histone H1, sterol 24-c-methyltransferase (SMT), Leishmania-specific hypothetical protein (LiHy), and Leishmania-specific antigenic protein (LSAP). To enhance vaccine immunogenicity, two resuscitation-promoting factor of Mycobacterium tuberculosis, RpfE and RpfB, were employed as adjuvants. All the aforesaid segments were joined using proper linkers. Homology modeling, followed by refinement and validation was performed to obtain a high-quality 3D structure of designed vaccine. Docking analyses and molecular dynamics (MD) studies indicated vaccine/TLR4 complex was in the stable form during simulation time. In sum, we expect our designed vaccine is able to induce humoral and cellular immune responses against L. infantum, and may be promising medication for VL, after in vitro and in vivo immunological assays.

Multi Epitope Peptide Vaccine against Human Parvovirus B19 Using Immuno-Informatics Approaches

Introduction: Human parvovirus B19 (B19V) is small non-enveloped, single-stranded DNA virus belong to genus Erythrovirus. B19V can cause erythema infectiosum (fifth disease), oligoarthritis, hydrops fetalis and a plastic crisis in patients with sickle cell anemia. A variety of vaccine strategies have been employed targeting immune responses. However their results were controversy with a limiting in availability of viral antigen. Since B19V replicates predominantly in erythroid progenitor cells of human bone marrow, this makes a peptide-based vaccines a promising strategy for development of vaccine against B19V with less allergenic and reactogenic responses. The aim of the present study was to design an efficient multi-epitope vaccine for human B19 virus using VP1 glycoprotein. Material and method: Thirty six sequences of VP1 glycoprotein were retrieved from NCBI database in December 2017 and aligned to determine the conservancy between the retrieved strains. The IEDB different analysis resources were used to predict epitopes that could act as promising peptides vaccine against parvovirus B19. The predicted epitopes were further assessed for population coverage against the whole world population. Results: The epitopes 214-PEVP-217, 675-GLHQPPP-681 and 554-SLRPGPVSQPYH-565 were found to be the most potential epitopes against B cells. For the T cell three epitopes namely 155-FRYSQLAKL-163, 302-CTISPIMGY-310 and 316-YLDFNALNL-324 showed high affinity to MHC-I alleles. The epitopes (core) 155-FRYSQLAKL-163, 438-FYVLEHSSF-446 and 404-WVYFPPQYA-412 showed high affinity to interact with MHC-II alleles. 155-FRYSQLAKL-163 and 438-FYVLEHSSF-446 showed high coverage for whole world population with percentage of 99.73% and 94.85% respectively. Conclusion: This study proposed eight epitopes for B and T cells that could be a powerful multi epitope vaccine against B19V. Particular concern directed towards the epitope 155-FRYSQLAKL-163 which demonstrated merits by reacting efficiently with both MHC-I and MHC-II alleles. Clinical trial is required to proof the efficacy of these epitopes as promising candidate vaccine against parvovirus B19.

Anti-GK1 antibodies damage Taenia crassiceps cysticerci through complement activation.

Taeniasis-cysticercosis, a zoonosis caused by Taenia solium, is prevalent in underdeveloped countries, where marginalization promotes its continued transmission. Pig cysticercosis, an essential stage for transmission, is preventable by vaccination. An efficient multiepitope vaccine against pig cysticercosis, S3Pvac, was developed. Previous studies showed that antibodies against one of the S3Pvac components, GK-1, are capable of damaging T. solium cysticerci, inhibiting their ability to transform into the adult stage in golden hamster gut. This study is aimed to evaluate one of the mechanisms that could mediate anti-GK-1 antibody-dependent protection. To this end, pig anti-GK-1 antibodies were produced and purified by using protein A. Proteomic analysis showed that the induced antibodies recognized the respective native cysticercal protein KE7 (Bobes et al. Infect Immun 85:e00395-17, 2017) and two additional T. solium proteins (endophilin B1 and Gp50). A new procedure to evaluate cysticercus viability, based on quantifying the cytochrome c released after parasite damage, was developed. Taenia crassiceps cysticerci were cultured in the presence of differing amounts of anti-GK-1 antibody and complement in a saturating concentration, along with the respective controls. Cysticercus viability was assessed by recording parasite motility, trypan blue exclusion, and cytochrome c levels in cysticercal soluble extract. Anti-GK-1 antibody significantly increased cysticercus damage as measured by all three methods. Parasite evaluation by electron microscopy after treatment with anti-GK-1 antibody plus complement demonstrated cysticercus damage as shorter, capsule-severed microtrichia; a decrease in glycocalyx length with respect to untreated cysts; and disaggregated desmosomes. These results demonstrate that anti-GK-1 antibodies damage cysticerci through classic complement activation.

A novel multi-epitope peptide vaccine against cancer: An in silico approach

Cancer immunotherapy has an outstanding position in cancer prevention and treatment. In this kind of therapy, the immune system is activated to eliminate cancerous cells. Multi-epitope peptide cancer vaccines are manifesting as the next generation of cancer immunotherapy. In the present study, we have implemented various strategies to design an efficient multi-epitope vaccine. CD8+ cytolytic T lymphocytes (CTLs) epitopes, which have a pivotal role in cellular immune responses, helper epitopes and adjuvant, are three crucial components of peptide vaccine. CTL epitopes were determined from two high immunogenic protein Wilms tumor-1 (WT1) and human papillomavirus (HPV) E7 by various servers, which apply different algorithms. CTL epitopes were linked together by AAY and HEYGAEALERAG motifs to enhance epitope presentation. Pan HLA DR-binding epitope (PADRE) peptide sequence and helper epitopes, which have defined from Tetanus toxin fragment C (TTFrC) by various servers, were used to induce CD4+ helper T lymphocytes (HTLs) responses. Additionally, helper epitopes were conjugated together via GPGPG motifs that stimulate HTL immunity. Heparin-Binding Hemagglutinin (HBHA), a novel TLR4 agonist was employed as an adjuvant to polarize CD4+ T cells toward T-helper 1 to induce strong CTL responses. Moreover, the EAAAK linker was introduced to N and C terminals of HBHA for efficient separation. 3D model of protein was generated and predicted B cell epitopes were determined from the surface of built structure. Our protein contains several linear and conformational B cell epitopes, which suggests the antibody triggering property of this novel vaccine. Hence, our final protein can be used for prophylactic or therapeutic usages, because it can potentially stimulate both cellular and humoral immune responses.