Journal of Immunology Research

Schistosoma japonicum is the most pathogenic causative form of schistosomiasis that causes a major health problem in its endemic countries. Until now, praziquantel is the only drug used to treat Schistosomiasis, but it does not prevent re-infection. So, repetition of the treatment is needed. Moreover, there is no effective vaccine against S. japonicum. Therefore, an urgent need for the development of vaccines is mandatory. This study aimed to analyze an immunogenic protein, Transitionally Controlled Tumor Protein (TCTP) using an immunoinformatics approach to design a universal peptide vaccine against Schistosoma japonicum. A set of 22 of TCTP sequences were retrieved from NCBI database. Conservancy of these sequences was tested and then conserved B cell and T cell epitopes were predicted using different tools available in IEBD. Epitopes having high scores in both B and T cell predicting tools were proposed. An epitope 129YEHYI133 was predicted as a most promising epitope with good prediction scores in surface accessibility and antigenicity. Besides that, epitopes 129YEHYIGESM 137and 92YLKAIKERL100 were predicted as the most promising epitopes concerning their binding to MHC I and MHC II allele respectively. The study revealed that our predicted epitopes could be used to develop an efficacious vaccine against Schistosoma japonicum in the future especially epitope YEHYIGESM as it is shared between MHC I and II alleles and overlapped with the most promising B cell epitope. Both in vitro and in vivo studies is recommended to confirm the efficacy of YEHYIGESM as a peptide vaccine.

Burkholderia pseudomallei, the gram-negative bacteria causing melioidosis, is becoming a serious threat to healthcare settings. In recent years, B. pseudomallei has been identified as an emerging and significant etiological agent responsible for localized pyogenic infections primarily observed in India and South Asia. At present, no vaccine against melioidosis is available in the treatment system. This study has undertaken an in-silico reverse vaccinology approach to design a novel multi-epitope vaccine for treating B. pseudomallei-mediated infections. B-cell and T-cell epitopes have been predicted and stitched to develop a multi-epitope vaccine. The predicted vaccine is found to be non-toxic, non-allergic, and immunogenic in nature. Immune simulation results indicate that the designed vaccine can generate an immune response resembling a real-life scenario. The 610 amino-acid long vaccine construct has been codon-optimized and could be cloned in the E. coli K12 system. These findings from this immunoinformatics study offer a foundation for developing a tailored, safe, and potent vaccine targeting B. pseudomallei.

BackgroundHelicobacter pylori coloniz the gastric mucosa of nearly half of the global population and is classified as a Group I carcinogen by the World Health Organization due to its strong association with gastric cancer. The growing prevalence of antibiotic-resistant H. pylori strains significantly compromises current therapeutic strategies, emphasizing the urgent need for effective prophylactic approaches. Research design and methodsIn this study, a novel multi-epitope vaccine was designed targeting H. pylori, incorporating epitopes from four key virulence proteins: BabB, SabB, SabA, and VacA. Using an immunoinformatics-guided structural vaccinology approach, B- and T-cell epitopes were predicted, prioritized based on immunogenicity, conservation, population coverage, and non-homology to human proteins, and assembled into the final vaccine construct. To enhance immunogenicity and specifically stimulate mucosal immune responses, the cholera toxin B subunit (CTB) was fused at the N-terminal via an EAAAK linker, a novel application in H. pylori multi-epitope vaccines. The PADRE universal epitope and additional linkers were incorporated to optimize epitope presentation and helper T-cell activation. ResultsComprehensive evaluations of physicochemical, antigenic, allergenic, and toxic properties were conducted, followed by secondary and tertiary structure modeling, refinement, and validation. Conformational B-cell epitopes were mapped, and molecular docking, binding affinity analysis, energy minimization, and molecular dynamics simulations confirmed structural stability and re-ceptor interactions. Codon optimization and in silico cloning predicted efficient expression in Escherichia coli, while immune simulations suggested robust humoral and cellular responses. ConclusionsThis study presents a promising multi-epitope vaccine candidate against H. pylori, offering a rational framework for future experimental validation and potential clinical application.

IntroductionTuberculosis (TB) is a serious disease with varying rates of mortality and morbidity among infected individuals which estimates for approximately two million deaths/year. The number of deaths could increase by 60% if left untreated. It mainly affects immune-compromised individuals and people of third world, due to poverty, low health standards, and inadequate medical care. It has varying range of manifestations that is affected by the host immune system response, the strain causing the infection, its virulence, and transmissibility.\n\nMaterials and methodsA total of 1750 Mycobacterium Tuberculosis PPE65 family protein strains were retrieved from National Center for Biotechnology Information (NCBI) database on March 2019 and several tools were used for the analysis of the T- and B-cell peptides and homology modelling.\n\nResults and conclusionFour strong epitope candidates had been predicted in this study for having good binding affinity to HLA alleles, good global population coverage percentages. These peptides are YAGPGSGPM, AELDASVAM, GRAFNNFAAPRYGFK and a single B-cell peptide YAGP.\n\nThis study uses immunoinformatics approach for the design of peptide based vaccines for M. tuberculosis. Peptide based vaccines are safer, more stable and less hazardous/allergenic when compared to conventional vaccines. In addition, peptide vaccines are less labouring, time consuming and cost efficient. The only weakness is the need to introduce an adjuvant to increase immunogenic stimulation of the vaccine recipient.

Schistosoma japonicum (Sj) infection induced liver granulomatous inflammation and fibrosis. As an active artemisinin analog, the implication of artemisitene (ATT) in schistosomiasis were unclear. Herein, we found that ATT significantly reduced the count of total adult worms and eggs, and increased the count of single males, injured the tegument in the surface of Sj adult worms & gynecophoral canal of males. The transcription of 98 genes in females and 48 genes in males were significantly changed, and these genes were closely related to cellular anatomical entity through gene ontology analysis. So, ATT might possess anti-parasite activity. Meanwhile, ATT treatment significantly lowered the level of glutamic oxaloacetic transaminase (AST) and glutamic pyruvic transaminase (ALT) in sera, the size of mesenteric lymph node, and granuloma, the collagen area and -SMA expression level in the liver. Liver transcriptome and multi-cytokines analysis indicated its immune regulation effect. Flow cytometry verified that the count of eosinophils in the liver were significantly increased, while the frequency of neutrophils, M1/M2 and Th1/Th2 index were significantly decreased. Therefore, we provided strong evidence that ATT has therapeutic potential through Sj clearance and anti-liver disease. Tegument development injury and immune regulation including type 2 immunity enhancement might be the mechanisms. Author summaryCurrently, there were still 290 million people worldwide who were infected by Schistosoma, and the treatment for schistosomiasis relies majorly on the use of a single drug-praziquantel. In this study, we described for the first time that artemisinin-derived artemisitene (ATT), chemically remarkably different from praziquantel, possessed the therapeutic effects on murine schistosomiasis japonica. ATT displayed both anti-Schistsosoma japonicum and anti-liver inflammation & liver fibrosis effect. Through RNA-seq and scanning electronic microscope of adult female & male worms from hepatoportal veins with or without ATT treatment, we found that the mechanisms of ATTs anti-parasites could be through injuring tegument development and then interrupting adult worms especially adult female worms clearance by immune cells such as eosinophils. Moreover, through RNA-seq of liver total RNA, ELISA of multi-cytokines in liver lysates and flow cytometry analysis of liver single cells, we found that the anti-liver diseases efficacy of ATT was associated with immune regulation especially type 2 immunity enhancement. Therefore, ATT possessed the therapeutic potential against schistosomiasis japonica and further researches were necessary for its future clinical use.

Schistosome infection showed protective effects against allergic airway inflammation (AAI). However, controversial findings exist especially regarding the timing of helminth infection and the underlying mechanisms. Moreover, most previous studies focused on understanding the preventive effect of schistosome infection on asthma (infection before allergen sensitization), while its therapeutic effects (infection after allergen sensitization) were rarely investigated. In this study, we investigated the therapeutic effects of schistosome infection on AAI using a mouse model of OVA induced asthma. To explore how the timing of schistosome infection influences its therapeutic effect, the mice were percutaneously infected with cercaria of Schistosoma japonicum at either 1 day before OVA induced asthma attack (infection at lung-stage during AAI) or 14 days before OVA induced asthma attack (infection at post lung-stage during AAI). We found that lung-stage schistosome infection significantly ameliorated OVA-induced AAI, whereas post lung-stage infection showed no therapeutic effect. Mechanistically, the lung-stage schistosome infection significantly upregulated the frequency of Treg, especially OVA specific Treg, in lung tissue, which negatively correlated with the level of OVA specific IgE. Depletion of Treg in vivo counteracted the therapeutic effect. Furthermore, transcriptomic analysis of lung tissue showed that lung-stage schistosome infection during AAI shaped the microenvironment to favor Treg induction. In conclusion, our data showed that lung-stage schistosome infection could relieve OVA induced asthma in a mouse model. The therapeutic effect was mediated by the upregulated OVA specific Treg which suppressed IgE production and Th2 cytokine secretion. Our results may facilitate the discovery of a new therapy for AAI. Author SummaryAsthma is an increasingly common disease especially in industrialized countries, which is still lack of an optimal therapy. The protective effect of schistosome infection against allergic asthma has been shown in previous studies, which represents a promising candidate immune intervention approach. However, controversial findings exist especially regarding the timing of helminth infection and the underlying mechanisms. In this study, we demonstrate that lung-stage schistosome infection could upregulate the frequency of allergen specific Treg, which significantly alleviated OVA induced allergic airway inflammation via inhibiting the production of IgE and Th2 cytokines. Our results proved the therapeutic effect of schistosome infection on allergic asthma. Moreover, we highlighted that lung-stage infection is essential for inducing allergen specific regulatory T cells in lung, which is the key mediator of the observed therapeutic effect. These findings shed new light on exploiting helminths or their derivatives to treat asthma and other allergic diseases.

Brucella abortus is a small aerobic, non-spore-forming, non-motile intracellular coccobacilli localized in the reproductive organs of host animals and causes acute or chronic disorders. It infects approximately 200 cases per 100,000 of the population and has become endemic in many countries. OmpW family protein is an outer membrane protein involved in the initial interaction between the pathogen and its host. This study predicts an effective epitope-based vaccine against OmpW family protein of Brucella abortus using immunoinformatics tools. Sequences were obtained from NCBI and prediction tests were accomplished to analyze possible epitopes for B and T cells. Seven B cell epitopes passed the antigenicity, accessibility and hydrophilicity tests. Forty-three MHC I epitopes were the most promising, while 438 from MHC II. For the population coverage, the epitopes covered 99.97% of the alleles worldwide excluding certain MHC II alleles. We recommend invivo and invitro studies to prove its effectiveness.

Salmonella infections are a global public health issue due to the high cost of illness surveillance, prevention, and treatment. In this study, we explored the core proteome in Salmonella to design a multi-epitope vaccine through Subtractive Proteomics and immunoinformatics approaches. A total of 2395 core proteins presents in 30 different strains of Salmonella (reference strain-NZ CP014051) were curated. Utilizing the subtractive proteomics approach on the Salmonella core proteome, Curlin major subunit A (CsgA) was selected as the vaccine candidate. csgA is a conserved gene that is related with biofilm formation. Immunodominant B and T cell epitopes from CsgA were predicted using numerous immunoinformatics tools. T lymphocyte epitopes had adequate population coverage and their corresponding MHC alleles showed significant binding scores after peptide-protein based molecular docking. Afterward, a multiepitope vaccine was constructed with peptide linkers and Human Beta Defensin-2 (as an adjuvant). The vaccine was found to be highly antigenic, non-toxic, non-allergic, and had physicochemical properties. Additionally, Molecular Dynamics Simulation and Immune Simulation demonstrated that the vaccine can bind with Toll Like Receptor 4 and elicit robust immune response. Using in vitro, in vivo, and clinical trials, our results would yield a Pan-Salmonella vaccine that will provide protection against various Salmonella species.

Tuberculosis is major challenge to the health care system with TB associated death rates increasing annually. Optimum management of TB (particularly latent or MDR cases) warrants use of immunological approaches like subunit or peptide-based vaccination for tailoring effector immunity in patients. Since MHC class I is a potent enhancer element of host immunity and effective in clearing large variety of intracellular pathogens or tumors. In this context, we explore whether MHC-I restricted peptides from clinical isolates of M. tuberculosis can be used as an adjuvant for augmenting host immune responses. In the present study, we have synthesized various peptides from clinical isolates of M. tuberculosis which were having high affinity for Class I MHC molecules as potential immune enhancer for T cell or iNKT cell populations. We have evaluated the immunogenic potential of various MHC class I restricted epitopes (Rv2588c, Rv1357, Rv0148, Rv2973, Rv2557 and Rv2445) which were derived from clinical isolates of M. tuberculosis on increased proliferation of T or iNKT cells, release of IFN gamma secreted by T cells as well as NO as indicative parameters of immuno-stimulation. As expected, FACS and ELISA data clearly revealed that these peptides were potentially immunogenic for PBMCs from both healthy as well as 10 HC PTB patients. Our data clearly demonstrated a significant immune response in the PBMC from w PTB patients over healthy individuals which mimicked booster response. Our cytokine and nitric oxide data further revealed the influence of these peptides on sensitizing innate immune response as well. SignificanceOur study demonstrates the significance of MHC class I restricted peptides from M. tuberculosis for inducing potential immunogenic responses in host that may qualify them as potent vaccine candidate. To the best of our knowledge this is the first immune monitoring protocol describing the impact of synthetic novel MHC class I restricted T-cell epitope (Rv2588c, Rv0148) on cell mediated and innate immune response in PBMC populations and suggests their potential as vaccine candidate

This paper presents an alternative vaccination platform that provides long-term cellular immune protection mediated by cytotoxic T-cells. The immune response via cellular immunity creates superior resistance to viral mutations, which are currently the greatest threat to the global vaccination campaign. Furthermore, we also propose a safer, more facile and physiologically appropriate immunization method using either intra-nasal or oral administration. The underlying technology is an adaptation of synthetic long peptides (SLPs) previously used in cancer immunotherapy. SLPs comprising HLA class I and class II epitopes are used to stimulate antigen cross-presentation and canonical class II presentation by dendritic cells. The result is a cytotoxic T cell-mediated prompt and specific immune response against the virus-infected epithelia and a rapid and robust virus clearance. Peptides isolated from COVID-19 convalescent patients were screened for the best HLA population coverage and were tested for toxicity and allergenicity. 3D peptide folding followed by molecular docking studies provided positive results, suggesting a favourable antigen presentation.

The global public health risk posed by Salmonella Kentucky, particularly due to the dissemination of antimicrobial resistance genes in human and animal populations, is rising. This serovar, widespread in Africa, has emerged as a notable cause of non-typhoidal gastroenteritis in humans. In this study, we utilized a bioinformatics approach to design a peptide-based vaccine targeting epitopes from the outer membrane proteins A, C, and F of Salmonella Kentucky, with the fliC protein from Salmonella Typhimurium serving as an adjuvant. Through this approach, we identified 14 CD8+ and 7 CD4+ T-cell epitopes, which are predicted to be restricted by various MHC class I and MHC class II alleles. When used in vaccine formulations, the predicted epitopes are expected to achieve a population coverage of 94.91%. Additionally, we identified seven highly immunogenic linear B-cell epitopes and three conformational B-cell epitopes. These T-cell and B-cell epitopes were then linked using appropriate linkers to create a multi-epitope vaccine (MEV). To enhance the immunogenicity of the peptide construct, the fliC protein from Salmonella Typhimurium was included at the N-terminal as an adjuvant. The resulting MEV construct demonstrated high structural quality and favorable physicochemical properties. Molecular docking studies with Toll-like receptors 1, 2, 4, and 5, followed by molecular dynamic simulations, suggested that the vaccine-receptor complexes are energetically feasible, stable, and robust. Immune simulation results showed that the MEV elicited significant responses, including IgG, IgM, CD8+ T-cells, CD4+ T-cells, and various cytokines (IFN-{gamma}, TGF-{beta}, IL-2, IL-10, and IL-12), along with a noticeable reduction in antigen levels. Despite these promising in silico results, further validation through preclinical and clinical trials is necessary to confirm the vaccines protective efficacy and safety.

Although several SARS-COV-2 vaccines have been approved, no one oral live vaccine is available. Here, an oral SARS-COV-2 RBD live vaccine containing LTB26 adjuvant has been developed. BALB/c mice are oral vaccinated with attenuated Salmonella typhimurium SL7207 containing pcDNA3.1-LTB26RBD or pcDNA3.1-RBD plasmids. The result shows that the high level of RBD specific antibody is produced in pcDNA3.1- LTB26RBD treatment. The mechanism indicates that LTB26 enhances RBD antibody production by significantly upregulating the activity of MHC II+ DCs and CD19+CD45+ B cells. LTB26 mutant is derived from heat-labile enterotoxin B subunit (LTB) wild type of Escherichia coli with enhanced immune adjuvanticity. Based on the pre-experiment result that SL7207 interferes the function of LTB26, the purified LTB26 was mixed with purified human rotavirus VP8 antigen to explore the mechanism of adjuvant. The results suggests that LTB26 enhances mucosal immune responses via increased of BCR and MHC II+ expression. Furthermore, LTB26 promotes both Th1 and Th2 cell mediated immunity. Therefore, LTB26 maybe a potent adjuvant for mucosal vaccine development in view of the safety of LTB26 than LT toxin.

Novel corona virus disease 2019 (COVID-19) is emerging as a pandemic situation and declared as a global health emergency by WHO. Due to lack of specific medicine and vaccine, viral infection has gained a frightening rate and created a devastating state across the globe. Here the authors have attempted to design epitope based potential peptide as a vaccine candidate using immunoinformatics approach. As of evidence from literatures, SARS-CoV-2 Spike protein is a key protein to initiate the viral infection within a host cell thus used here as a reasonable vaccine target. We have predicted a 9-mer peptide as representative of both B-cell and T-cell epitopic region along with suitable properties such as antigenic and non-allergenic. To its support, strong molecular interaction of the predicted peptide was also observed with MHC molecules and Toll Like receptors. The present study may helpful to step forward in the development of vaccine candidates against COVID-19. O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

Schistosoma Mansoni represents an important tropical disease that can cause schistosomiasis mostly in Africa and Middle East with high mortality rates. Moreover, no vaccine against it exists. This study predicts an effective epitope-based vaccine against Fructose 1,6 Bisphosphate Aldolase (FBA) enzyme of Schistosoma Mansoni using immunoinformatics approaches. FBA is important for production of energy required for different schistosome activities and survival. The sequences were retrieved from NCBI and several prediction tests were conducted to analyze possible epitopes for B-cell, T-cell MHC class I and II. Tertiary structure of the most promising epitopes was obtained. Two epitopes showed high binding affinity for B-cells, while four epitopes showed high binding affinity for MHCI and MHCII. The results were promising to formulate a vaccine with more than 99.5% population coverage. We hope that these promising epitopes serves as a preventive measure for the disease in the future and recommend invivo and invitro studies.

Sepsis is a severe life-threatening condition caused by a dysregulated host response to infection. So far, there are no pharmacotherapies to stop sepsis. Salbutamol, a commonly used {beta}2-adrenoreceptor agonist, has found to be potential in regulating immune response dysfunction and exert anti-inflammatory effect. However, salbutamol exists two isomers. R-isomer exhibits the therapeutic effect and clinical benefit, while S-isomer proves to be detrimental rather than benign. So, in this study, we investigated the preventive and therapeutic effect of R-salbutamol (R-sal), S-salbutamol (S-sal) or racemic mixture in a mouse model of lipopolysaccharide (LPS)-induced sepsis. Dexamethasone (Dex) was set as comparison. The results showed that R-sal markedly improved seven-day survival rate of septic mice both administered before or after LPS. Whereas Dex showed toxic and accelerated the death of septic mice when given before LPS injection. Lung histological examination and lung function assay revealed that LPS challenge resulted in acute lung damage, including inflammatory cell infiltration, thickened alveolar septa and congestion, and decreased minute volume in septic mice. R-sal pretreatment efficiently inhibited these changes, accompanying by markedly reduced lung MPO level, serum cytokines levels and lactate release and significantly restored the lymphocytes and suppressed the percentage of monocytes. Racemic mixture exhibited diminished effects while S-sal showed enhanced cytokines release. In addition, R-sal pretreatment showed a better improvement in prognostic pulmonary function at day4 in survived mice than that of Rac-sal. Collectively, our results indicate the potential benefit of R-sal for sepsis and sepsis-induced lung injury.

A new coronavirus SARS-CoV-2 has caused over 9.2 million infection cases and 475758 deaths worldwide. Due to the rapid dissemination and the unavailability of specific therapy, there is a desperate need for vaccines to combat the epidemic of SARS-CoV-2. An in silico approach based on the available virus 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 showed stable hydrogen bonds of epitopes with their corresponding HLA alleles. When four vaccine peptide candidates from the spike protein of SARS-CoV-2 were selected to immunize mice, a significantly larger amount of IgG in serum as well as an increase of CD19+ cells in ILNs was observed in peptide-immunized mice compared to the control mice. The ratio of IFN-{gamma}-secreting lymphocytes in CD4+ or CD8+ cells in the peptides-immunized mice were higher than that in the control mice. There were also a larger number of IFN-{gamma}-secreting T cells in spleen in the peptides-immunized mice. This study screened antigenic B-cell and T-cell epitopes in all encoded proteins of SARS-CoV-2, and further designed multi-epitope based peptide vaccine against viral structural proteins. The obtained vaccine peptides successfully elicited specific humoral and cellular immune responses in mice. Primate experiments and clinical trial are urgently required to validate the efficacy and safety of these vaccine peptides. ImportanceSo far, a new coronavirus SARS-CoV-2 has caused over 9.2 million infection cases and 475758 deaths worldwide. Due to the rapid dissemination and the unavailability of specific therapy, there is a desperate need for vaccines to combat the epidemic of SARS-CoV-2. Different from the development approaches for traditional vaccines, the development of our peptide vaccine is faster and simpler. In this study, we performed an in silico approach to identify the antigenic B-cell epitopes and human-leukocyte-antigen (HLA) restricted T-cell epitopes, and designed a panel of multi-epitope peptide vaccines. The resulting SARS-CoV-2 multi-epitope peptide vaccine could elicit specific humoral and cellular immune responses in mice efficiently, displaying its great potential in our fight of COVID-19.

Legionella pneumophila, the causative agent of a serious type of pneumonia (lung infection) called Legionnaires disease. It is emerging as an antibacterial resistant strain day by day. Hence, the identification of novel drug targets and vaccine candidates is essential to fight against this pathogen. Herein attempts were taken through subtractive genomics approach on complete proteome of L. pneumophila to address the challenges of multidrug resistance. A total 2930 proteins from L. pneumophila proteome were investigated through diverse subtractive proteomics approaches, e.g., identification of human non-homologous and pathogen-specific essential proteins, druggability and anti-target analysis, prediction of subcellular localization, human microbiome non-homology screening, protein-protein interactions studies in order to find out effective drug and vaccine targets. Only 3 were identified that fulfilled all these criteria and proposed as novel drug targets against L. pneumophila. Furthermore, outer membrane protein TolB was identified as potential vaccine target with better antigenicity score and allowed for further in silico analysis to design a unique multiepitope subunit vaccine against it. Antigenicity and transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis, and molecular docking approach were adopted to generate the most potent epitopes. The final vaccine was constructed by the combination of highly immunogenic epitopes along with suitable adjuvant and linkers. The designed vaccine construct showed higher binding interaction with different MHC molecules and human immune TLR2 receptors with minimum deformability at molecular level. The translational potency and microbial expression of the vaccine protein was also analyzed using pET28a(+) vector. The present study aids in the development of novel therapeutics and vaccine candidates for efficient treatment of the infections caused by Legionella pneumophila. However, further wet lab-based investigations and in vivo trials are highly recommended to experimentally validate our prediction.

The recent Coronavirus Disease 2019 (COVID-19) causes an immense health crisis to global public health. The COVID-19 is the etiologic agent of a recently arose disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Presently, there is no vaccine available against this emerged viral disease. Therefore, it is indeed a need of the hour to develop an effectual and safe vaccine against this decidedly pandemic disease. In the current study, we collected SARS-CoV-2 genome which is prominent in India against human host, further more using reverse vaccinology here we claim effective vaccine candidates that can be mile stone in battle against COVID19. This novel study divulged one promising antigenic peptide GVYFASTEK from surface glycoprotein (protein accession no. - QIA98583.1) of SARS-CoV-2, which was predicated to be interacted with MHC alleles and showed up to 90% conservancy and high value of antigenicity. Subsequently, the molecular docking and simulation studies were verified molecular interaction of this prime antigenic peptide with the residues of HLA-A*11-01 allele for MHC Class I. After vigorous analysis, this peptide was predicted to be suitable epitope which is capable to induce the strong cell-mediated immune response against the SARS-CoV-2. Consequences from the current study could facilitate selecting SARS-CoV-2 epitopes for vaccine production pipelines in the immediate future. This novel research will certainly pave the way for a fast, reliable and virtuous platform to provide timely countermeasure of this dangerous pandemic disease, COVID-19.

Burkholderia mallei, a facultative intracellular Gram-negative pathogen, is the causative agent of glanders that primarily affects solipeds and sporadically transmitted to humans. Current interventions mainly rely on antibiotics; however, increasing resistance and the lack of a licensed vaccine further complicate disease management. In the present study, a consensus-based computational framework was employed on the B. mallei turkey2 proteome. Total 59 proteins - including porins, TonB receptors, autotransporters, and efflux components - were identified as surface exposed outer membrane {beta}-barrel (OMBB) proteins that were used to design a multi-epitope vaccine (MEV) construct. B- and T-cell epitopes were predicted from 59 proteins, and ten epitopes each of cytotoxic T-lymphocyte (CTL), helper T-lymphocyte (HTL), and B-cell were chosen based on their antigenicity, non-allergenicity, non-toxicity, surface accessibility, and conservation across 32 B. mallei strains. The MEV was included with suitable adjuvants at the N-terminus to enhance its immunogenicity. The 780 amino acid MEV construct was predicted to be antigenic, and soluble upon overexpression with 62.69% random coils, while the rest formed -helices and {beta}-strands. The tertiary structure of the MEV was generated and subsequently validated, indicating good structural quality. Molecular docking of the MEV with toll-like receptor 4 (TLR4) demonstrated strong affinity, and molecular dynamics simulation confirmed the structural stability of the MEV-TLR4 complex. In-silico immune simulation showed the capability of MEV to induce a strong immune response. The study proposes an MEV construct by utilizing surface exposed OMBB proteins which directly interact with the host and serve as effective immunogenic targets against B. mallei infection. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=80 SRC="FIGDIR/small/727591v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@10cd6d8org.highwire.dtl.DTLVardef@1ed3f0borg.highwire.dtl.DTLVardef@c6173forg.highwire.dtl.DTLVardef@1204f73_HPS_FORMAT_FIGEXP M_FIG C_FIG

A novel Coronavirus (SARS-COV-2) has now become a global pandemic. Considering the severity of infection and the associated mortalities, there is an urgent need to develop an effective preventive measure against this virus. In this study, we have designed a novel vaccine construct using computational strategies. Spike (S) glycoprotein is the major antigenic component that trigger the host immune responses. Detailed investigation of S protein with various immunoinformatics tools enabled us to identify 5 MHC I and 5 MHC II B-cell derived T-cell epitopes with VaxiJen score > 1 and IC50 value < 100nM. These epitopes were joined with a suitable adjuvant and appropriate linkers to form a multi-epitope based vaccine construct. Further, in silico testing of the vaccine construct for its antigenicity, allergenicity, solubility, and other physicochemical properties showed it to be safe and immunogenic. Suitable tertiary structure of the vaccine protein was generated using 3Dpro of SCRATCH suite, refined with GalaxyRefine, and validated with ProSA, PROCHECK, and ERRAT server. Finally, molecular docking studies were performed to ensure a favorable binding affinity between the vaccine construct and TLR3 receptor. The designed multi-epitope vaccine showed potential to elicit specific immune responses against the SARS-COV-2. However, further wet lab validation is necessary to confirm the actual effectiveness, safety and immunogenic potency of the vaccine construct against derived in this study.