Human Coronavirus Spike Protein Based Multi-Epitope Vaccine against COVID-19 and Potential Future Zoonotic Coronaviruses by Using Immunoinformatic Approaches
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ABSTRACT:
SUBMITTER: Baloch Z
PROVIDER: S-EPMC9323133 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:(1) Background: The monkeypox virus is a zoonotic orthopox DNA virus that is closely linked to the virus. In light of the growing concern about this virus, the current research set out to use bioinformatics and immunoinformatics to develop a potential vaccine against the virus. (2) Methods: A multiepitope vaccine was constructed from the B-cell and T-cell epitopes of the MPXVgp181 strain using adjuvant and different linkers. The constructed vaccine was predicted for antigenicity, allergenicity, toxicity, and population coverage. In silico immune simulation studies were also carried out. Expression analysis and cloning of the constructed vaccine was carried out in the pET-28a(+) vector using snapgene. (3) Results: The constructed vaccine was predicted to be antigenic, non-allergenic, and non-toxic. It was predicted to have excellent global population coverage and produced satisfactory immune response. The in silico expression and cloning studies were successful in E. coli, which makes the vaccine construct suitable for mass production in the pharmaceutical industry. (4) Conclusion: The constructed vaccine is based on the B-cell and T-cell epitopes obtained from the MPXVgp181 strain. This research can be useful in developing a vaccine to combat the monkeypox virus globally after performing in-depth in vitro and in vivo studies.
| S-EPMC9786588 | biostudies-literature
Project description:Through 4 June 2021, COVID-19 has caused over 172.84 million cases of infection and 3.71 million deaths worldwide. Due to its rapid dissemination and high mutation rate, it is essential to develop a vaccine harboring multiple epitopes and efficacious against multiple variants to prevent the immune escape of SARS-CoV-2. An in silico approach based on the viral genome was applied to identify 19 high-immunogenic B-cell epitopes and 499 human leukocyte antigen (HLA)-restricted T-cell epitopes. Thirty multi-epitope peptide vaccines were designed by iNeo-Suite and manufactured by solid-phase synthesis. Docking analysis confirmed stable hydrogen bonds of epitopes with their corresponding HLA alleles. When four peptide candidates derived from the spike protein of SARS-CoV-2 were selected to immunize mice, a significantly larger amount of total IgG in serum, as well as an increase of CD19+ cells in the inguinal lymph nodes, were observed in the peptide-immunized mice compared to the control. The ratios of IFN-γ-secreting lymphocytes in CD4+ or CD8+ T-cells in the peptide-immunized mice were higher than those in the control mice. There were also a larger number of IFN-γ-secreting T-cells in the spleens of peptide-immunized mice. The peptide vaccines in this study successfully elicited antigen-specific humoral and cellular immune responses in mice. To further validate the safety and efficacy of this vaccine, animal studies using a primate model, as well as clinical trials in humans, are required.
| S-EPMC8230658 | biostudies-literature
Project description: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.
| S-EPMC9266094 | biostudies-literature
Project description:Human African trypanosomiasis (HAT) is a neglected tropical disease that is caused by flagellated parasites of the genus Trypanosoma. HAT imposes a significant socio-economic burden on many countries in sub-Saharan Africa and its control is hampered by several drawbacks ranging from the ineffectiveness of drugs, complex dosing regimens, drug resistance, and lack of a vaccine. Despite more than a century of research and investigations, the development of a vaccine to tackle HAT is still challenging due to the complex biology of the pathogens. Advancements in computational modeling coupled with the availability of an unprecedented amount of omics data from different organisms have allowed the design of new generation vaccines that offer better antigenicity and safety profile. One of such new generation approaches is a multi-epitope vaccine (MEV) designed from a collection of antigenic peptides. A MEV can stimulate both cellular and humoral immune responses as well as avoiding possible allergenic reactions. Herein, we take advantage of this approach to design a MEV from conserved hypothetical plasma membrane proteins of Trypanosoma brucei gambiense, the trypanosome subspecies that is responsible for the west and central African forms of HAT. The designed MEV is 402 amino acids long (41.5 kDa). It is predicted to be antigenic, non-toxic, to assume a stable 3D conformation, and to interact with a key immune receptor. In addition, immune simulation foresaw adequate immune stimulation by the putative antigen and a lasting memory. Therefore, the designed chimeric vaccine represents a potential candidate that could be used to target HAT.
| S-EPMC9576565 | biostudies-literature
Project description:Achromobacter xylosoxidans, previously identified as Alcaligenes xylosoxidans, is a rod-shaped, flagellated, non-fermenting Gram-negative bacterium that has the ability to cause diverse infections in humans. As a part of its intrinsic resistance to different antibiotics, Achromobacter spp. is also increasingly becoming resistant to Carbapenems. Lack of knowledge regarding the pathogen's clinical features has led to limited efforts to develop countermeasures against infection. The current study utilized an immunoinformatic method to map antigenic epitopes (Helper T cells, B-cell and Cytotoxic-T cells) to design a vaccine construct. We found that 20 different epitopes contribute significantly to immune response instigation that was further supported by physicochemical analysis and experimental viability. The safety profile of our vaccine was tested for antigenicity, allergenicity, and toxicity against all the identified epitopes before they were used as vaccine candidates. The disulfide engineering was carried out in an area of high mobility to increase the stability of vaccine proteins. In order to determine if the constructed vaccine is compatible with toll-like receptor, the binding affinity of vaccine was investigated via molecular docking approach. With the in silico expression in host cells and subsequent immune simulations, we were able to detect the induction of both arms of the immune response, i.e., humoral response and cytokine induced response. To demonstrate its safety and efficacy, further experimental research is necessary.
| S-EPMC9309517 | biostudies-literature
Project description:COVID-19 has recently become the most serious threat to public health, and its prevalence has been increasing at an alarming rate. The incubation period for the virus is ~1-14 days and all age groups may be susceptible to a fatality rate of about 5.9%. COVID-19 is caused by a novel single-stranded, positive (+) sense RNA beta coronavirus. The development of a vaccine for SARS-CoV-2 is an urgent need worldwide. Immunoinformatics approaches are both cost-effective and convenient, as in silico predictions can reduce the number of experiments needed. In this study, with the aid of immunoinformatics tools, we tried to design a multi-epitope vaccine that can be used for the prevention and treatment of COVID-19. The epitopes were computed by using B cells, cytotoxic T lymphocytes (CTL), and helper T lymphocytes (HTL) base on the proteins of SARS-CoV-2. A vaccine was devised by fusing together the B cell, HTL, and CTL epitopes with linkers. To enhance the immunogenicity, the β-defensin (45 mer) amino acid sequence, and pan-HLA DR binding epitopes (13aa) were adjoined to the N-terminal of the vaccine with the help of the EAAAK linker. To enable the intracellular delivery of the modeled vaccine, a TAT sequence (11aa) was appended to C-terminal. Linkers play vital roles in producing an extended conformation (flexibility), protein folding, and separation of functional domains, and therefore, make the protein structure more stable. The secondary and three-dimensional (3D) structure of the final vaccine was then predicted. Furthermore, the complex between the final vaccine and immune receptors (toll-like receptor-3 (TLR-3), major histocompatibility complex (MHC-I), and MHC-II) were evaluated by molecular docking. Lastly, to confirm the expression of the designed vaccine, the mRNA of the vaccine was enhanced with the aid of the Java Codon Adaptation Tool, and the secondary structure was generated from Mfold. Then we performed in silico cloning. The final vaccine requires experimental validation to determine its safety and efficacy in controlling SARS-CoV-2 infections.
| S-EPMC7399176 | biostudies-literature
Project description:Cervical cancer, caused by human papillomavirus (HPV), is the fourth most common type of cancer among women worldwide. While HPV prophylactic vaccines are available, they have no therapeutic effects and do not clear up existing infections. This study aims to design a therapeutic vaccine against cervical cancer using reverse vaccinology. In this study, the E6 and E7 oncoproteins from HPV16 were chosen as the target antigens for epitope prediction. Cytotoxic T lymphocytes (CTL) and helper T lymphocytes (HTL) epitopes were predicted, and the best epitopes were selected based on antigenicity, allergenicity, and toxicity. The final vaccine construct was composed of the selected epitopes, along with the appropriate adjuvant and linkers. The multi-epitope vaccine was evaluated in terms of physicochemical properties, antigenicity, and allergenicity. The tertiary structure of the vaccine construct was predicted. Furthermore, several analyses were also carried out, including molecular docking, molecular dynamics (MD) simulation, and in silico cloning of the vaccine construct. The results showed that the final proposed vaccine could be considered an effective therapeutic vaccine for HPV; however, in vitro and in vivo experiments are required to validate the efficacy of this vaccine candidate.
| S-EPMC8196015 | biostudies-literature
Project description:Coxsackievirus B (CVB) is one of the major viral pathogens of human myocarditis and cardiomyopathy without any effective preventive measures; therefore, it is necessary to develop a safe and efficacious vaccine against CVB. Immunoinformatics methods are both economical and convenient as in-silico simulations can shorten the development time. Herein, we design a novel multi-epitope vaccine for the prevention of CVB by using immunoinformatics methods. With the help of advanced immunoinformatics approaches, we predicted different B-cell, cytotoxic T lymphocyte (CTL), and helper T lymphocyte (HTL) epitopes, respectively. Subsequently, we constructed the multi-epitope vaccine by fusing all conserved epitopes with appropriate linkers and adjuvants. The final vaccine was found to be antigenic, non-allergenic, and stable. The 3D structure of the vaccine was then predicted, refined, and evaluated. Molecular docking and dynamics simulation were performed to reveal the interactions between the vaccine with the immune receptors MHC-I, MHC-II, TLR3, and TLR4. Finally, to ensure the complete expression of the vaccine protein, the sequence of the designed vaccine was optimized and further performed in-silico cloning. In conclusion, the molecule designed in this study could be considered a potential vaccine against CVB infection and needed further experiments to evaluate its safety and efficacy.
| S-EPMC9682020 | biostudies-literature
Project description:Outbreaks of monkeypox virus infections have imposed major health concerns worldwide, with high morbidity threats to children and immunocompromised adults. Although repurposed drugs and vaccines are being used to curb the disease, the evolving traits of the virus, exhibiting considerable genetic dynamicity, challenge the limits of a targeted treatment. A pan-genome-based reverse vaccinology approach can provide fast and efficient solutions to resolve persistent inconveniences in experimental vaccine design during an outbreak-exigency. The approach encompassed screening of available monkeypox whole genomes (n = 910) to identify viral targets. From 102 screened viral targets, viral proteins L5L, A28, and L5 were finalized based on their location, solubility, and antigenicity. The potential T-cell and B-cell epitopes were extracted from the proteins using immunoinformatics tools and algorithms. Multiple vaccine constructs were designed by combining the epitopes. Based on immunological properties, chemical stability, and structural quality, a novel multi-epitopic vaccine construct, V4, was finalized. Flexible-docking and coarse-dynamics simulation portrayed that the V4 had high binding affinity towards human HLA-proteins (binding energy < -15.0 kcal/mol) with low conformational fluctuations (<1 Å). Thus, the vaccine construct (V4) may act as an efficient vaccine to induce immunity against monkeypox, which encourages experimental validation and similar approaches against emerging viral infections.
| S-EPMC9695528 | biostudies-literature
Project description:BackgroundInfectious bronchitis (IB) is a highly contagious respiratory disease in chickens and produces economic loss within the poultry industry. This disease is caused by a single stranded RNA virus belonging to Cronaviridae family. This study aimed to design a potential multi-epitopes vaccine against infectious bronchitis virus spike protein (S). Protein characterization was also performed for IBV spike protein.MethodsThe present study used various tools in Immune Epitope Database (IEDB) to predict conserved B and T cell epitopes against IBV spike (S) protein that may perform a significant role in provoking the resistance response to IBV infection.ResultsIn B cell prediction methods, three epitopes ( 1139 KKSSYY 1144 , 1140 KSSYYT 1145 , 1141 SSYYT 1145 ) were selected as surface, linear and antigenic epitopes.Many MHCI and MHCII epitopes were predicted for IBV S protein. Among them 982YYITARDMY990 and 983 YITARDMYM 991 epitopes displayed high antigenicity, no allergenicity and no toxicity as well as great linkage with MHCI and MHCII alleles. Moreover, docking analysis of MHCI epitopes produced strong binding affinity with BF2 alleles.ConclusionFive conserved epitopes were expected from spike glycoprotein of IBV as the best B and T cell epitopes due to high antigenicity, no allergenicity and no toxicity. In addition, MHC epitopes showed great linkage with MHC alleles as well as strong interaction with BF2 alleles. These epitopes should be designed and incorporated and then tested as multi-epitope vaccine against IBV.
| S-EPMC7450164 | biostudies-literature