Designing a multi-epitope vaccine candidate to combat MERS-CoV by employing an immunoinformatics approach

AbstractCurrently, no approved vaccine is available against the Middle East respiratory syndrome coronavirus (MERS-CoV), which causes severe respiratory disease. The spike glycoprotein is typically considered a suitable target for MERS-CoV vaccine candidates. A computational strategy can be used to design an antigenic vaccine against a pathogen. Therefore, we used immunoinformatics and computational approaches to design a multi-epitope vaccine that targets the spike glycoprotein of MERS-CoV. After using numerous immunoinformatics tools and applying several immune filters, a poly-epitope vaccine was constructed comprising cytotoxic T-cell lymphocyte (CTL)-, helper T-cell lymphocyte (HTL)-, and interferon-gamma (IFN-γ)-inducing epitopes. In addition, various physicochemical, allergenic, and antigenic profiles were evaluated to confirm the immunogenicity and safety of the vaccine. Molecular interactions, binding affinities, and the thermodynamic stability of the vaccine were examined through molecular docking and dynamic simulation approaches, during which we identified a stable and strong interaction with Toll-like receptors (TLRs). In silico immune simulations were performed to assess the immune-response triggering capabilities of the vaccine. This computational analysis suggested that the proposed vaccine candidate would be structurally stable and capable of generating an effective immune response to combat viral infections; however, experimental evaluations remain necessary to verify the exact safety and immunogenicity profile of this vaccine.

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Exogenous Interleukin-33 Contributes to Protective Immunity via Cytotoxic T-Cell Priming against Mucosal Influenza Viral Infection

Viruses ◽

10.3390/v11090840 ◽

2019 ◽

Vol 11 (9) ◽

pp. 840 ◽

Cited By ~ 1

Author(s):

Chae Won Kim ◽

Hye Jee Yoo ◽

Jang Hyun Park ◽

Ji Eun Oh ◽

Heung Kyu Lee

Keyword(s):

Immune Response ◽

Influenza Virus ◽

T Cell ◽

Viral Infections ◽

Influenza Infection ◽

Influenza Virus Infection ◽

Respiratory Illness ◽

Cytotoxic T Cell ◽

Antiviral Immune Response ◽

Cytotoxic T Cell Responses

Influenza is an infectious respiratory illness caused by the influenza virus. Though vaccines against influenza exist, they have limited efficacy. To additionally develop effective treatments, there is a need to study the mechanisms of host defenses from influenza viral infections. To date, the mechanism by which interleukin (IL)-33 modulates the antiviral immune response post-influenza infection is unclear. In this study, we demonstrate that exogenous IL-33 enhanced antiviral protection against influenza virus infection. Exogenous IL-33 induced the recruitment of dendritic cells, increased the secretion of pro-inflammatory cytokine IL-12, and promoted cytotoxic T-cell responses in the local microenvironment. Thus, our findings suggest a role of exogenous IL-33 in the antiviral immune response against influenza infection.

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A Computational Reverse Vaccinology Approach for the Design and Development of Multi-Epitopic Vaccine Against Avian Pathogen Mycoplasma gallisepticum

Frontiers in Veterinary Science ◽

10.3389/fvets.2021.721061 ◽

2021 ◽

Vol 8 ◽

Author(s):

Susithra Priyadarshni Mugunthan ◽

Harish Mani Chandra

Keyword(s):

T Cell ◽

Vaccine Candidate ◽

Mycoplasma Gallisepticum ◽

Chronic Respiratory Disease ◽

Economic Losses ◽

Cytotoxic T Cell ◽

Bacterial Disease ◽

Epitope Vaccine ◽

Antigenic Proteins ◽

Avian Pathogen

Avian mycoplasma is a bacterial disease causing chronic respiratory disease (CRD) in poultry industries with high economic losses. The eradication of this disease still remains as a challenge. A multi-epitope prophylactic vaccine aiming the antigenic proteins of Mycoplasma gallisepticum can be a capable candidate to eradicate this infection. The present study is focused to design a multi-epitope vaccine candidate consisting of cytotoxic T-cell (CTL), helper T-cell (HTL), and B-cell epitopes of antigenic proteins, using immunoinformatics strategies. The multi-epitopic vaccine was designed, and its tertiary model was predcited, which was further refined and validated by computational tools. After initial validation, molecular docking was performed between multi-epitope vaccine construct and chicken TLR-2 and 5 receptors, which predicted effective binding. The in silico results specify the structural stability, precise specificity, and immunogenic response of the designed multi-epitope vaccine, and it could be an appropriate vaccine candidate for the M. gallisepticum infection.

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Potentiation by a novel alkaloid glycoside adjuvant of a protective cytotoxic T cell immune response specific for a preerythrocytic malaria vaccine candidate antigen

Vaccine ◽

10.1016/s0264-410x(01)00166-9 ◽

2001 ◽

Vol 19 (30) ◽

pp. 4153-4161 ◽

Cited By ~ 27

Author(s):

Karen G Heal ◽

Nadeem A Sheikh ◽

Michael R Hollingdale ◽

W.John W Morrow ◽

Andrew W Taylor-Robinson

Keyword(s):

Immune Response ◽

T Cell ◽

Malaria Vaccine ◽

Vaccine Candidate ◽

Cytotoxic T Cell ◽

Cell Immune Response ◽

Vaccine Candidate Antigen ◽

Malaria Vaccine Candidate ◽

Candidate Antigen

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Immuno-informatics approach for multi-epitope vaccine designing against SARS-CoV-2

10.1101/2020.07.23.218529 ◽

2020 ◽

Cited By ~ 1

Author(s):

Souvik Banerjee ◽

Kaustav Majumder ◽

Gerardo Jose Gutierrez ◽

Debkishore Gupta ◽

Bharti Mittal

Keyword(s):

Immune Response ◽

T Cell ◽

B Cell ◽

In Silico ◽

Dynamics Simulation ◽

Cytotoxic T Cell ◽

Epitope Vaccine ◽

B Cell Epitopes ◽

Corona Virus ◽

The World

AbstractThe novel Corona Virus Disease 2019 (COVID-19) pandemic has set the fatality rates ablaze across the world. So, to combat this disease, we have designed a multi-epitope vaccine from various proteins of Severe Acute Respiratory Syndrome Corona virus 2 (SARS-CoV-2) with an immuno-informatics approach, validated in silico to be stable, non-allergic and antigenic. Cytotoxic T-cell, helper T-cell, and B-cell epitopes were computationally predicted from six conserved protein sequences among four viral strains isolated across the world. The T-cell epitopes, overlapping with the B-cell epitopes, were included in the vaccine construct to assure the humoral and cell-mediated immune response. The beta-subunit of cholera toxin was added as an adjuvant at the N-terminal of the construct to increase immunogenicity. Interferon-gamma inducing epitopes were even predicted in the vaccine. Molecular docking and binding energetics studies revealed strong interactions of the vaccine with immune-stimulatory toll-like receptors (TLR) −2, 3, 4. Molecular dynamics simulation of the vaccine ensured in vivo stability in the biological system. The immune simulation of vaccine evinced elevated immune response. The efficient translation of the vaccine in an expression vector was assured utilizing in silico cloning approach. Certainly, such a vaccine construct could reliably be effective against COVID-19.

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Reduction of memory cytotoxic T cell numbers by heterologous viral infections: A mathematical model

Immunology Letters ◽

10.1016/s0165-2478(97)87852-2 ◽

1997 ◽

Vol 56 (1-3) ◽

pp. 254

Author(s):

K Takumi

Keyword(s):

Mathematical Model ◽

T Cell ◽

Viral Infections ◽

Cytotoxic T Cell ◽

Cell Numbers

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Modelling the interplay between the CD4$$^{+}$$/CD8$$^{+}$$ T-cell ratio and the expression of MHC-I in tumours

Journal of Mathematical Biology ◽

10.1007/s00285-021-01622-1 ◽

2021 ◽

Vol 83 (1) ◽

Author(s):

Christian John Hurry ◽

Alexander Mozeika ◽

Alessia Annibale

Keyword(s):

Immune Response ◽

T Cell ◽

Critical Level ◽

Cell Infiltration ◽

Cytotoxic T Cell ◽

Mhc I ◽

Cell Ratio ◽

T Cell Infiltration ◽

Immunological Mechanisms ◽

Tcr Repertoire

AbstractDescribing the anti-tumour immune response as a series of cellular kinetic reactions from known immunological mechanisms, we create a mathematical model that shows the CD4$$^{+}$$ + /CD8$$^{+}$$ + T-cell ratio, T-cell infiltration and the expression of MHC-I to be interacting factors in tumour elimination. Methods from dynamical systems theory and non-equilibrium statistical mechanics are used to model the T-cell dependent anti-tumour immune response. Our model predicts a critical level of MHC-I expression which determines whether or not the tumour escapes the immune response. This critical level of MHC-I depends on the helper/cytotoxic T-cell ratio. However, our model also suggests that the immune system is robust against small changes in this ratio. We also find that T-cell infiltration and the specificity of the intra-tumour TCR repertoire will affect the critical MHC-I expression. Our work suggests that the functional form of the time evolution of MHC-I expression may explain the qualitative behaviour of tumour growth seen in patients.

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Biomolecular Materials: Self-Assembled Peptide Amphiphile Micelles Containing a Cytotoxic T-Cell Epitope Promote a Protective Immune Response In Vivo (Adv. Mater. 28/2012)

Advanced Materials ◽

10.1002/adma.201290170 ◽

2012 ◽

Vol 24 (28) ◽

pp. 3709-3709

Author(s):

Matthew Black ◽

Amanda Trent ◽

Yulia Kostenko ◽

Joseph Saeyong Lee ◽

Colleen Olive ◽

...

Keyword(s):

Immune Response ◽

T Cell ◽

Cell Epitope ◽

Protective Immune Response ◽

Cytotoxic T Cell ◽

T Cell Epitope ◽

Peptide Amphiphile ◽

Self Assembled

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Cytotoxic T-cell-based vaccine against SARS-CoV2: a hybrid immunoinformatic approach

10.1101/2021.09.26.461851 ◽

2021 ◽

Author(s):

Alexandru Tîrziu ◽

Virgil Păunescu

Keyword(s):

Immune Response ◽

T Cell ◽

Cytotoxic T Cells ◽

Vaccination Campaign ◽

Hla Class I ◽

Class Ii ◽

Docking Studies ◽

Cytotoxic T Cell ◽

Cross Presentation ◽

Canonical Class

AbstractThis 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.

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