Development of a novel platform of virus-like particle (VLP)-based vaccine against COVID-19 by exposing epitopes: an immunoinformatics approach.
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ABSTRACT:
SUBMITTER: Ghorbani A
PROVIDER: S-EPMC7556220 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The newly emerged mosquito-borne Zika virus poses a major public challenge due to its ability to cause significant birth defects and neurological disorders. The impact of sexual transmission is unclear but raises further concerns about virus dissemination. No specific treatment or vaccine is currently available, thus the development of a safe and effective vaccine is paramount. Here we describe a novel strategy to assemble Zika virus-like particles (VLPs) by co-expressing the structural (CprME) and non-structural (NS2B/NS3) proteins, and demonstrate their effectiveness as vaccines. VLPs are produced in a suspension culture of mammalian cells and self-assembled into particles closely resembling Zika viruses as shown by electron microscopy studies. We tested various VLP vaccines and compared them to analogous compositions of an inactivated Zika virus (In-ZIKV) used as a reference. VLP immunizations elicited high titers of antibodies, as did the In-ZIKV controls. However, in mice the VLP vaccine stimulated significantly higher virus neutralizing antibody titers than comparable formulations of the In-ZIKV vaccine. The serum neutralizing activity elicited by the VLP vaccine was enhanced using a higher VLP dose and with the addition of an adjuvant, reaching neutralizing titers greater than those detected in the serum of a patient who recovered from a Zika infection in Brazil in 2015. Discrepancies in neutralization levels between the VLP vaccine and the In-ZIKV suggest that chemical inactivation has deleterious effects on neutralizing epitopes within the E protein. This along with the inability of a VLP vaccine to cause infection makes it a preferable candidate for vaccine development.
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Project description: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.
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Project description:Infectious laryngotracheitis virus (ILTV) is a gallid herpesvirus type 1, a member of the genus Iltovirus. It causes an infection in the upper respiratory tract mainly trachea which results in significant economic losses in the poultry industry worldwide. Vaccination against ILTV produced latent infected carriers' birds, which become a source of virus transmission to nonvaccinated flocks. Thus this study aimed to design safe multiepitopes vaccine against glycoprotein B of ILT virus using immunoinformatic tools. Forty-four sequences of complete envelope glycoprotein B were retrieved from GenBank of National Center for Biotechnology Information (NCBI) and aligned for conservancy by multiple sequence alignment (MSA). Immune Epitope Database (IEDB) analysis resources were used to predict and analyze candidate epitopes that could act as a promising peptide vaccine. For B cell epitopes, thirty-one linear epitopes were predicted using Bepipred. However eight epitopes were found to be on both surface and antigenic epitopes using Emini surface accessibility and antigenicity, respectively. Three epitopes ( 190 KKLP 193 , 386 YSSTHVRS 393 , and 317 KESV 320 ) were proposed as B cell epitopes. For T cells several epitopes were interacted with MHC class I with high affinity and specificity, but the best recognized epitopes were 118 YVFNVTLYY 126 , 335 VSYKNSYHF 343 , and 622 YLLYEDYTF 630 . MHC-II binding epitopes, 301 FLTDEQFTI 309 , 277 FLEIANYQV 285 , and 743 IASFLSNPF 751 , were proposed as promising epitopes due to their high affinity for MHC-II molecules. Moreover the docked ligand epitopes from MHC-1 molecule exhibited high binding affinity with the receptors; BF chicken alleles (BF2 2101 and 0401) expressed by the lower global energy of the molecules. In this study nine epitopes were predicted as promising vaccine candidate against ILTV. In vivo and in vitro studies are required to support the effectiveness of these predicted epitopes as a multipeptide vaccine through clinical trials.
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Project description:The Zika virus disease, also known as Zika fever is an arboviral disease that became epidemic in the Pacific Islands and had spread to 18 territories of the Americas in 2016. Zika virus disease has been linked to several health problems such as microcephaly and the Guillain-Barré syndrome, but to date, there has been no vaccine available for Zika. Problems related to the development of a vaccine include the vaccination target, which covers pregnant women and children, and the antibody dependent enhancement (ADE), which can be caused by non-neutralizing antibodies. The peptide vaccine was chosen as a focus of this study as a safer platform to develop the Zika vaccine. In this study, a collection of Zika proteomes was used to find the best candidates for T- and B-cell epitopes using the immunoinformatics approach. The most promising T-cell epitopes were mapped using the selected human leukocyte antigen (HLA) alleles, and further molecular docking and dynamics studies showed a good peptide-HLA interaction for the best major histocompatibility complex-II (MHC-II) epitope. The most promising B-cell epitopes include four linear peptides predicted to be cross-reactive with T-cells, and conformational epitopes from two proteins accessible by antibodies in their native biological assembly. It is believed that the use of immunoinformatics methods is a promising strategy against the Zika viral infection in designing an efficacious multiepitope vaccine.
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Project description:Teschovirus A belongs to the family Picornaviridae and is a causal agent of the disease Teschovirus encephalomyelitis and other infections that remain asymptomatic. The present study was performed to design epitope-based peptide vaccine against Teschovirus A by identifying the potential T cell and B-cell epitopes from capsid proteins (VP1, VP3 and VP2) of the virus using reverse vaccinology and immunoinformatics approaches. In the current study, hexapeptide T-cell and octapeptide B-cell epitopes were analyzed for immunogenicity, antigenicity and hydrophilicity scores of each epitope. Each potential epitope was further characterized using ExPASy-ProtParam and Antimicrobial Peptide Database (APD3) tools for determining various physical and chemical parameters of the epitope. One linear hexapeptide T-cell epitope, i.e., RPVNDE (epitope position 77-82) and one linear octapeptide B-cell epitope, i.e., AYSRSHPQ (236-243) were identified from the viral capsid protein as they possess the capability to raise effective immunogenic reaction in the host organism against the virus. Pharmaceutical industries could harness the results of this investigation to develop epitope-based peptide vaccines by loading the identified epitopes in combination with targeting signal peptides of T-cells and B-cells and then inserting the combination into virus like particle (vlp) or constructing subunit vaccines for further trial.
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Project description:Infectious bursal disease virus is the causative agent of infectious bursal disease (Gumboro disease), a highly contagious immunosuppressive disease of chicken with a substantial economic impact on small- and large-scale poultry industries worldwide. Currently, live attenuated vaccines are widely used to control the disease in chickens despite their issues with safety (immunosuppression and bursal atrophy) and efficiency (breaking through the maternally-derived antibody titer). To overcome the drawbacks, the current study has, for the first time, attempted to construct a computational model of a multiepitope based vaccine candidate against infectious bursal disease virus, which has the potential to overcome the safety and protection issues found in the existing live-attenuated vaccines. The current study used a reverse vaccinology based immunoinformatics approach to construct the vaccine candidate using major and minor capsid proteins of the virus, VP2 and VP3, respectively. The vaccine construct was composed of four CD8+ epitopes, seven CD4+ T-cell epitopes, 11 B-cell epitopes and a Cholera Toxin B adjuvant, connected using appropriate flexible peptide linkers. The vaccine construct was evaluated as antigenic with VaxiJen Score of 0.6781, immunogenic with IEDB score of 2.89887 and non-allergenic. The 55.64 kDa construct was further evaluated for its physicochemical characteristics, which revealed that it was stable with an instability index of 16.24, basic with theoretical pI of 9.24, thermostable with aliphatic index of 86.72 and hydrophilic with GRAVY score of -0.256. The docking and molecular dynamics simulation studies of the vaccine construct with Toll-like receptor-3 revealed fair structural interaction (binding affinity of -295.94 kcal/mol) and complex stability. Further, the predicted induction of antibodies and cytokines by the vaccine construct indicated the possible elicitation of the host's immune response against the virus. The work is a significant attempt to develop next-generation vaccines against the infectious bursal disease virus though further experimental studies are required to assess the efficacy and protectivity of the proposed vaccine candidate in vivo.
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Project description: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.
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Project description:BackgroundMonkeypox virus is an enveloped DNA virus that belongs to Poxviridae family. The virus is transmitted from rodents to primates via infected body fluids, skin lesions, and respiratory droplets. After being infected with virus, the patients experience fever, myalgia, maculopapular rash, and fluid-filled blisters. It is necessary to differentiate monkeypox virus from other poxviruses during diagnosis which can be appropriately envisioned via DNA analysis from swab samples. During small outbreaks, the virus is treated with therapies administered in other orthopoxviruses infections and does not have its own specific therapy and vaccine. Consequently, in this article, two potential peptides have been designed.MethodsFor the purpose of designing a vaccine, protein sequences were retrieved followed by the prediction of B- and T-cell epitopes. Afterward, vaccine structures were predicted which were docked with toll-like receptors. The docked complexes were analyzed with iMODS. Moreover, vaccine constructs nucleotide sequences were optimized and expressed in silico.ResultsCOP-B7R vaccine construct (V1) has antigenicity score of 0.5400, instability index of 29.33, z-score of - 2.11-, and 42.11% GC content whereas COP-A44L vaccine construct (V2) has an antigenicity score of 0.7784, instability index of 23.33, z-score of - 0.61, and 48.63% GC content. It was also observed that COP-A44L can be expressed as a soluble protein in Escherichia coli as compared to COP-B7R which requires a different expression system.ConclusionThe obtained results revealed that both vaccine constructs show satisfactory outcomes after in silico investigation and have significant potential to prevent the monkeypox virus. However, COP-A44L gave better results.
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Project description:Visceral leishmaniasis (VL) infection is mostly caused by Leishmania donovani and affects countries worldwide. Despite the need for a safe and effective vaccine against leishmaniasis due to the increased drug resistance, however, no vaccine has yet been licensed for clinical use. This study revolves around the immunoinformatics approach to design a multi-epitope vaccine against VL infection. In this case, the proteome of L. donovani has been investigated, and three host non-homologous and antigenic extracellular secretory proteins have been identified as potential vaccine candidates with low transmembrane helices (≤ 1). The multi-epitope subunit vaccine construct consists of T-cell (cytotoxic T-lymphocyte (CTL) and helper T-lymphocyte (HTL)) epitopes accompanied by appropriate adjuvant and linkers. A 372-amino acid vaccine construct has been established with specific characteristics, such as soluble, stable, antigenic, non-allergenic, non-toxic, and non-host homologous. Besides, the tertiary structure of the designed vaccine was modeled and validated. Also, the stability and affinity of the vaccine- TLR4 complex were confirmed by using molecular docking and molecular dynamics (MD) simulation. In addition, in silico immunization assay showed the efficiency of this candidate vaccine to stimulate an effective immune response. Furthermore, the refined vaccine was optimized and cloned in the pET28a (+) vector, and its successful expression was confirmed virtually. However, the experimental validation is required to verify the multi-epitope vaccine efficacy against VL infection.
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Project description:Japanese encephalitis virus (JEV) is the leading cause of epidemic encephalitis in Asia, and vaccination is the most effective way to prevent JE. Although several licensed vaccines were widely used, there is still a demand for developing safer, cheaper, and more effective JE vaccines. In the current study, a virus-like particle (VLP) vaccine candidate containing the envelope structural protein of JEV expressed by the Pichia pastoris was assembled in vitro. It elicited a robust humoral and cellular immune response in mice model, conferring immunodeficient mice complete protection against lethal doses of JEV challenge. Furthermore, pigs immunized with VLP alone without adjuvant via intramuscular produced high neutralizing antibodies against JEV. Consequently, this study showed a new design of JEV subunit vaccine based on VLP strategy and demonstrated the potential for clinical application.
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