Towards A Novel Multi-Epitopes Chimeric Vaccine for Simulating Strong Immune Responses and Protection against Morganella morganii

Morganella morganii is one of the main etiological agents of hospital-acquired infections and no licensed vaccine is available against the pathogen. Herein, we designed a multi-epitope-based vaccine against M. morganii. Predicted proteins from fully sequenced genomes of the pathogen were subjected to a core sequences analysis, followed by the prioritization of non-redundant, host non-homologous and extracellular, outer membrane and periplasmic membrane virulent proteins as vaccine targets. Five proteins (TonB-dependent siderophore receptor, serralysin family metalloprotease, type 1 fimbrial protein, flagellar hook protein (FlgE), and pilus periplasmic chaperone) were shortlisted for the epitope prediction. The predicted epitopes were checked for antigenicity, toxicity, solubility, and binding affinity with the DRB*0101 allele. The selected epitopes were linked with each other through GPGPG linkers and were joined with the cholera toxin B subunit (CTBS) to boost immune responses. The tertiary structure of the vaccine was modeled and blindly docked with MHC-I, MHC-II, and Toll-like receptors 4 (TLR4). Molecular dynamic simulations of 250 nanoseconds affirmed that the designed vaccine showed stable conformation with the receptors. Further, intermolecular binding free energies demonstrated the domination of both the van der Waals and electrostatic energies. Overall, the results of the current study might help experimentalists to develop a novel vaccine against M. morganii.

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In silico approach for designing of a multi-epitope based vaccine against novel Coronavirus (SARS-COV-2)

10.1101/2020.03.31.017459 ◽

2020 ◽

Cited By ~ 4

Author(s):

Ratnadeep Saha ◽

Burra V L S Prasad

Keyword(s):

Immune Responses ◽

In Silico ◽

Tertiary Structure ◽

Preventive Measure ◽

Docking Studies ◽

T Cell Epitopes ◽

Mhc I ◽

Host Immune Responses ◽

Global Pandemic ◽

Novel Coronavirus

AbstractA 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.

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Prediction of the Omp16 Epitopes for the Development of an Epitope-based Vaccine Against Brucellosis

Infectious Disorders - Drug Targets ◽

10.2174/1871526518666180709121653 ◽

2019 ◽

Vol 19 (1) ◽

pp. 36-45 ◽

Cited By ~ 3

Author(s):

Marzieh Rezaei ◽

Mohammad Rabbani-khorasgani ◽

Sayyed Hamid Zarkesh-Esfahani ◽

Rahman Emamzadeh ◽

Hamid Abtahi

Keyword(s):

Immune Responses ◽

B Cell ◽

Dairy Products ◽

Bioinformatics Analysis ◽

Epitope Prediction ◽

Animal Husbandry ◽

Zoonotic Diseases ◽

Recombinant Vaccines ◽

Protective Capacity ◽

Tertiary Structures

Background:Brucellosis is an infectious disease caused by Brucella bacteria that cause disease in animals and humans. Brucellosis is one of the most common zoonotic diseases transmitted from animals-to-human through direct contact with infected animals and also consumption of unpasteurized dairy products. Due to the wide incidence of brucellosis in Iran and economical costs in industrial animal husbandry, Vaccination is the best way to prevent this disease. All of the available commercial vaccines against brucellosis are derived from live attenuated strains of Brucella but because of the disadvantage of live attenuated vaccines, protective subunit vaccine against Brucella may be a good candidate for the production of new recombinant vaccines based on Brucella Outer Membrane Protein (OMP) antigens. In the present study, comprehensive bioinformatics analysis has been conducted on prediction software to predict T and B cell epitopes, the secondary and tertiary structures and antigenicity of Omp16 antigen and the validation of used software confirmed by experimental results.Conclusion:The final epitope prediction results have proposed that the three epitopes were predicted for the Omp16 protein with antigenicity ability. We hypothesized that these epitopes likely have the protective capacity to stimulate both the B-cell and T-cell mediated immune responses and so may be effective as an immunogenic candidate for the development of an epitope-based vaccine against brucellosis.

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Design of a multi-epitope vaccine against cervical cancer using immunoinformatics approaches

Scientific Reports ◽

10.1038/s41598-021-91997-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Samira Sanami ◽

Fatemeh Azadegan-Dehkordi ◽

Mahmoud Rafieian-Kopaei ◽

Majid Salehi ◽

Maryam Ghasemi-Dehnoo ◽

...

Keyword(s):

Cervical Cancer ◽

T Lymphocytes ◽

Tertiary Structure ◽

Therapeutic Vaccine ◽

Epitope Prediction ◽

Therapeutic Effects ◽

Epitope Vaccine ◽

In Vivo Experiments

AbstractCervical 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.

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Effects of Recombinant Cholera Toxin B Subunit (rCTB) on Cellular Immune Responses: Enhancement of Delayed-Type Hypersensitivity Following Intranasal Co-Administration ofMycobacterium bovis-BCG with rCTB

Microbiology and Immunology ◽

10.1111/j.1348-0421.2004.tb03536.x ◽

2004 ◽

Vol 48 (6) ◽

pp. 457-463 ◽

Cited By ~ 6

Author(s):

Jun-ichi Maeyama ◽

Masanori Isaka ◽

Yoko Yasuda ◽

Keiko Matano ◽

Kazunori Morokuma ◽

...

Keyword(s):

Immune Responses ◽

Cholera Toxin ◽

Delayed Type Hypersensitivity ◽

Cholera Toxin B Subunit ◽

Toxin B ◽

Cholera Toxin B ◽

B Subunit ◽

Cellular Immune Responses ◽

Cellular Immune

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Dimorphism of HLA-E and its Disease Association

International Journal of Molecular Sciences ◽

10.3390/ijms20215496 ◽

2019 ◽

Vol 20 (21) ◽

pp. 5496 ◽

Cited By ~ 5

Author(s):

Leonid Kanevskiy ◽

Sofya Erokhina ◽

Polina Kobyzeva ◽

Maria Streltsova ◽

Alexander Sapozhnikov ◽

...

Keyword(s):

Bacterial Infections ◽

Tertiary Structure ◽

Hla Class I ◽

Surface Expression ◽

Class I ◽

Human Populations ◽

Cytotoxic Lymphocytes ◽

Main Function ◽

Mhc I ◽

High Level

HLA-E is a nonclassical member of the major histocompatibility complex class I gene locus. HLA-E protein shares a high level of homology with MHC Ia classical proteins: it has similar tertiary structure, associates with β2-microglobulin, and is able to present peptides to cytotoxic lymphocytes. The main function of HLA-E under normal conditions is to present peptides derived from the leader sequences of classical HLA class I proteins, thus serving for monitoring of expression of these molecules performed by cytotoxic lymphocytes. However, opposite to multiallelic classical MHC I genes, HLA-E in fact has only two alleles—HLA-E*01:01 and HLA-E*01:03—which differ by one nonsynonymous amino acid substitution at position 107, resulting in an arginine in HLA-E*01:01 (HLA-ER) and glycine in HLA-E*01:03 (HLA-EG). In contrast to HLA-ER, HLA-EG has higher affinity to peptide, higher surface expression, and higher thermal stability of the corresponding protein, and it is more ancient than HLA-ER, though both alleles are presented in human populations in nearly equal frequencies. In the current review, we aimed to uncover the reason of the expansion of the younger allele, HLA-ER, by analysis of associations of both HLA-E alleles with a number of diseases, including viral and bacterial infections, cancer, and autoimmune disorders.

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Design of Epitope-Based Peptide Vaccine against Pseudomonas aeruginosa Fructose Bisphosphate Aldolase Protein Using Immunoinformatics

Journal of Immunology Research ◽

10.1155/2020/9475058 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Mustafa Elhag ◽

Ruaa Mohamed Alaagib ◽

Nagla Mohamed Ahmed ◽

Mustafa Abubaker ◽

Esraa Musa Haroun ◽

...

Keyword(s):

Pseudomonas Aeruginosa ◽

Peptide Vaccine ◽

Multidrug Resistant ◽

Fructose Bisphosphate ◽

Mhc I ◽

Mhc Ii ◽

Fructose Bisphosphate Aldolase ◽

Hospital Acquired

Pseudomonas aeruginosa is a common pathogen that is responsible for serious hospital-acquired infections, ventilator-associated pneumonia, and various sepsis syndromes. Also, it is a multidrug-resistant pathogen recognized for its ubiquity and its intrinsically advanced antibiotic-resistant mechanisms. It usually affects immunocompromised individuals but can also infect immunocompetent individuals. There is no vaccine against it available till now. This study predicts an effective epitope-based vaccine against fructose bisphosphate aldolase (FBA) of Pseudomonas aeruginosa using immunoinformatics tools. The protein sequences were obtained from NCBI, and prediction tests were undertaken to analyze possible epitopes for B and T cells. Three B cell epitopes passed the antigenicity, accessibility, and hydrophilicity tests. Six MHC I epitopes were found to be promising, while four MHC II epitopes were found promising from the result set. Nineteen epitopes were shared between MHC I and II results. For the population coverage, the epitopes covered 95.62% worldwide excluding certain MHC II alleles. We recommend in vivo and in vitro studies to prove its effectiveness.

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P04.06 mucosal immunization with a cDC1-targeted CTA1 adjuvant vaccine confers protection against melanoma metastasis

Journal for ImmunoTherapy of Cancer ◽

10.1136/jitc-2020-itoc7.75 ◽

2020 ◽

Vol 8 (Suppl 2) ◽

pp. A39.1-A39

Author(s):

M Arabpour ◽

S Paul ◽

R Kiffin ◽

HG Wiktorin ◽

K Hellstrand ◽

...

Keyword(s):

T Cells ◽

Dendritic Cells ◽

T Cell ◽

Immune Responses ◽

Pulmonary Metastases ◽

T Cell Immunity ◽

Metastasis Formation ◽

Mhc I ◽

Mhc Ii ◽

Cell Immunity

BackgroundSpecific targeting of anti-cancer vaccines to dendritic cells (DCs) has been shown to mount efficient immune responses against tumor cells. Classical CD103+dendritic cells (also called cDC1) have an inherent ability to cross-present antigens to CD8+ cytotoxic T cells. Here we have explored an anti-tumor vaccine that specifically targets cDC1 cells for protection against and elimination of metastatic melanoma. The vaccine contains the cholera toxin A1 subunit (CTA1) adjuvant and is targeted to cDC1 cells through an anti-CD103 single chain antibody (CD103 scFv).Material and MethodsC57BL/6 mice were injected with wild type or ovalbumin (OVA) expressing B16 melanoma cells either subcutaneously (s.c.) to establish solid tumors, or intravenously (i.v.) to allow the formation of pulmonary metastases. Before or after establishment of tumors, mice were intra-nasally inoculated with a vaccine composed of a CD103 scFv element fused to the adjuvant CTA1 and the MHC I H2kd-restricted OVA epitope SIINFEKL together with the MHC II H2kd-restricted OVA epitope p323 or just the p323 peptide alone (i.e. CTA1-SIINFEKL-p323-CD103 and CTA1-p323-CD103, respectively). Control mice were inoculated with PBS. The growth of solid tumors was carefully monitored and the development of pulmonary metastases was determined 2–3 weeks after tumor cell injection. In addition, antigen-specific T cell immunity following intranasal immunization was evaluated.ResultsTargeting MHC I and MHC II tumor cell epitopes to cDC1, via CD103 ScFv, in conjunction with the CTA1 adjuvant elicited strong tumor specific and protective CD8+ T cell responses as well as CD4+ T cell immunity. Immunization with the CTA1-SIINFEKL-p323-CD103 vaccine significantly reduced the growth of established solid B16F1-OVA melanomas (P<0.001) and potently prevented metastasis formation (P<0.01). Control immunizations with the CTA1-p323-CD103 vaccine tended to reduce metastasis, but tumor-specific CD8+ T cells were required for full therapeutic protection.ConclusionTargeting tumor specific CD8+ T cell epitopes to cDC1, in the context of a powerful adjuvant such as CTA1, leads to the development of efficient anti-tumor immune responses. Our results point towards the utility of cDC1-targeted vaccines in the treatment of established tumors or as a means to prevent metastasis formation.Disclosure InformationM. Arabpour: None. S. Paul: None. R. Kiffin: None. H.G. Wiktorin: None. K. Hellstrand: None. N. Lycke: None. A. Martner: None.

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Mechanism of enhancement of the immune responses to influenza vaccine with cholera toxin B subunit and a trace amount of holotoxin

Vaccine ◽

10.1016/0264-410x(95)98253-7 ◽

1995 ◽

Vol 13 (4) ◽

pp. 339-341 ◽

Cited By ~ 15

Author(s):

S TAMURA

Keyword(s):

Immune Responses ◽

Influenza Vaccine ◽

Cholera Toxin ◽

Trace Amount ◽

Cholera Toxin B Subunit ◽

Toxin B ◽

Cholera Toxin B ◽

B Subunit

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Cellular and genetic restrictions in the immunoregulatory activity of alpha-fetoprotein. I. Selective inhibition of anti-Ia-associated proliferative reactions.

Journal of Experimental Medicine ◽

10.1084/jem.147.3.667 ◽

1978 ◽

Vol 147 (3) ◽

pp. 667-683 ◽

Cited By ~ 27

Author(s):

A B Peck ◽

R A Murgita ◽

H Wigzell

Keyword(s):

T Cell ◽

Immune Responses ◽

Selective Inhibition ◽

Immunosuppressive Agent ◽

Alpha Fetoprotein ◽

Region Gene ◽

Mhc I ◽

D Region

Alpha-fetoprotein (AFP), a major alpha-globulin component of fetal and newborn sera, has earlier been shown to exert significant immunosuppressive activity in vitro on T-dependent-immune responses. In the present investigation we have examined the effects of AFP on the recognition and proliferation of T lymphocytes responding in mixed leukocyte culture against histocompatibility-associated alloantigens. Fetal-derived AFP could be shown to exert differential effects on both primary and secondary responses ranging from strong inhibition to occasional enhancement, depending on the stimulating antigens. Proliferative responses against major histocompatibility complex (MHC) I region determinants, mediated predominantly by Ly 1 + cells, were markedly suppressed. Suppression was also observed in responses against Mls locus products, an antigenic system whose recognition requires concomitant recognition of I region gene products on the stimulating cells. In contrast, responses against MHC K or D region determinants, mediated predominantly by Ly 2 + cells, were generally unaffected by AFP. Similarly, non-MHC loci alloantigens distinct from Mls locus products also induced T-cell proliferation which was refractive to suppression by AFP. Because neither Ly 1 + nor Ly 2 + cells responding in this latter situation could be inhibited by AFP, we concluded that the mere fact that a T cell expresses a particular Ly phenotype does not predetermine sensitivity to AFP-induced suppression. In any case, AFP exerts a highly selective suppressive activity on I region-associated immune responses. These data may help to resolve the present controversy over the possibility that AFP has an in vivo relevance as an immunosuppressive agent by pointing out the importance of selecting proper genetic situations for study.

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