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Development of innovative multi-epitope mRNA vaccine against Pseudomonas aeruginosa using in silico approaches.

ABSTRACT: The rising issue of antibiotic resistance has made treating Pseudomonas aeruginosa infections increasingly challenging. Therefore, vaccines have emerged as a viable alternative to antibiotics for preventing P. aeruginosa infections in susceptible individuals. With its superior accuracy, high efficiency in stimulating cellular and humoral immune responses, and low cost, mRNA vaccine technology is quickly replacing traditional methods. This study aimed to design a novel mRNA vaccine by using in silico approaches against P. aeruginosa. The research team identified five surface and antigenic proteins and selected their appropriate epitopes with immunoinformatic tools. These epitopes were then examined for toxicity, allergenicity and homology. The researchers also checked their presentation and identification by major histocompatibility complex cells and other immune cells through valuable tools like molecular docking. They subsequently modeled a multi-epitope protein and optimized it. The mRNA was analyzed in terms of structure and stability, after which the immune system's response against the new vaccine was simulated. The results indicated that the designed mRNA construct could be an effective and promising vaccine that requires laboratory and clinical trials.

SUBMITTER: Asadinezhad M

PROVIDER: S-EPMC10772946 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Development of innovative multi-epitope mRNA vaccine against Pseudomonas aeruginosa using in silico approaches.

Asadinezhad Maryam M Khoshnood Saeed S Asadollahi Parisa P Ghafourian Sobhan S Sadeghifard Nourkhoda N Pakzad Iraj I Zeinivand Yasaman Y Omidi Nazanin N Hematian Ali A Kalani Behrooz Sadeghi BS

Briefings in bioinformatics 20231101 1

The rising issue of antibiotic resistance has made treating Pseudomonas aeruginosa infections increasingly challenging. Therefore, vaccines have emerged as a viable alternative to antibiotics for preventing P. aeruginosa infections in susceptible individuals. With its superior accuracy, high efficiency in stimulating cellular and humoral immune responses, and low cost, mRNA vaccine technology is quickly replacing traditional methods. This study aimed to design a novel mRNA vaccine by using in si ...[more]

PMID: 38189537

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Project description:Multidrug-resistant Pseudomonas aeruginosa is one of the worldwide health problems involved in elevated mortality and morbidity. Therefore, it is important to find a therapeutic for this pathogen. In the present study, we have designed a chimeric vaccine against P. aeruginosa with the help of comparative proteomics and reverse vaccinology approaches. Using comparative subtractive proteomic analysis of 1,191 proteomes of P. aeruginosa, a total of twenty unique non-redundant proteomes were selected. In these proteomes, fifteen outer membrane proteins (OMPs) of P. aeruginosa were selected based on the basis of hydrophilicity, non-secretory nature, low transmembrane helix (<1), essentiality, virulence, pathway association, antigenic, and protein-protein network analysis. Reverse vaccinology approach was used to identify antigenic and immunogenic MHC class I, MHC class II and B cell epitopes present in the selected OMPs that can enhance T cell and B cell mediated immunogenicity. The selected epitopes were shortlisted based on their allergenicity, toxicity potentials, solubility, and hydrophilicity analysis. Immunogenic peptides were used to design a multi-epitope vaccine construct. Immune-modulating adjuvants and PADRE (Pan HLA-DR epitopes) sequence were added with epitopes sequence to enhance the immunogenicity. All the epitopes, adjuvants and PADRE sequence were joined by linkers. The designed vaccine constructs (VT1, VT2, VT3, and VT4) were analyzed by their physiochemical properties using different tools. Selected chimeric vaccine constructs (VT1, VT3, and VT4) were further shortlisted by their docking score with different HLA alleles. The final selected VT4 construct was docked with TLR4/MD2 complex and confirmed by molecular dynamics simulation studies. The final vaccine VT-4 construct was in-silico cloned in pET28a. Therefore, the designed construct VT4 may be studied to control the interaction of P. aeruginosa with host and infection caused by P. aeruginosa.

Project description:BackgroundCervical cancer is the fourth most common cancer affecting women and is caused by human Papillomavirus (HPV) infections that are sexually transmitted. There are currently commercially available prophylactic vaccines that have been shown to protect vaccinated individuals against HPV infections, however, these vaccines have no therapeutic effects for those who are previously infected with the virus. The current study's aim was to use immunoinformatics to develop a multi-epitope vaccine with therapeutic potential against cervical cancer.ResultsIn this study, T-cell epitopes from E5 and E7 proteins of HPV16/18 were predicted. These epitopes were evaluated and chosen based on their antigenicity, allergenicity, toxicity, and induction of IFN-γ production (only in helper T lymphocytes). Then, the selected epitopes were sequentially linked by appropriate linkers. In addition, a C-terminal fragment of Mycobacterium tuberculosis heat shock protein 70 (HSP70) was used as an adjuvant for the vaccine construct. The physicochemical parameters of the vaccine construct were acceptable. Furthermore, the vaccine was soluble, highly antigenic, and non-allergenic. The vaccine's 3D model was predicted, and the structural improvement after refinement was confirmed using the Ramachandran plot and ProSA-web. The vaccine's B-cell epitopes were predicted. Molecular docking analysis showed that the vaccine's refined 3D model had a strong interaction with the Toll-like receptor 4. The structural stability of the vaccine construct was confirmed by molecular dynamics simulation. Codon adaptation was performed in order to achieve efficient vaccine expression in Escherichia coli strain K12 (E. coli). Subsequently, in silico cloning of the multi-epitope vaccine was conducted into pET-28a ( +) expression vector.ConclusionsAccording to the results of bioinformatics analyses, the multi-epitope vaccine is structurally stable, as well as a non-allergic and non-toxic antigen. However, in vitro and in vivo studies are needed to validate the vaccine's efficacy and safety. If satisfactory results are obtained from in vitro and in vivo studies, the vaccine designed in this study may be effective as a therapeutic vaccine against cervical cancer.

Project description:BackgroundInfluenza A virus is one of the leading causes of annual mortality. The emerging of novel escape variants of the influenza A virus is still a considerable challenge in the annual process of vaccine production. The evolution of vaccines ranks among the most critical successes in medicine and has eradicated numerous infectious diseases. Recently, multi-epitope vaccines, which are based on the selection of epitopes, have been increasingly investigated.ResultsThis study utilized an immunoinformatic approach to design a recombinant multi-epitope vaccine based on a highly conserved epitope of hemagglutinin, neuraminidase, and membrane matrix proteins with fewer changes or mutate over time. The potential B cells, cytotoxic T lymphocytes (CTL), and CD4 T cell epitopes were identified. The recombinant multi-epitope vaccine was designed using specific linkers and a proper adjuvant. Moreover, some bioinformatics online servers and datasets were used to evaluate the immunogenicity and chemical properties of selected epitopes. In addition, Universal Immune System Simulator (UISS) in silico trial computational framework was run after influenza exposure and recombinant multi-epitope vaccine administration, showing a good immune response in terms of immunoglobulins of class G (IgG), T Helper 1 cells (TH1), epithelial cells (EP) and interferon gamma (IFN-g) levels. Furthermore, after a reverse translation (i.e., convertion of amino acid sequence to nucleotide one) and codon optimization phase, the optimized sequence was placed between the two EcoRV/MscI restriction sites in the PET32a+ vector.ConclusionsThe proposed "Recombinant multi-epitope vaccine" was predicted with unique and acceptable immunological properties. This recombinant multi-epitope vaccine can be successfully expressed in the prokaryotic system and accepted for immunogenicity studies against the influenza virus at the in silico level. The multi-epitope vaccine was then tested with the Universal Immune System Simulator (UISS) in silico trial platform. It revealed slight immune protection against the influenza virus, shedding the light that a multistep bioinformatics approach including molecular and cellular level is mandatory to avoid inappropriate vaccine efficacy predictions.

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Development of innovative multi-epitope mRNA vaccine against Pseudomonas aeruginosa using in silico approaches.

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Development of innovative multi-epitope mRNA vaccine against Pseudomonas aeruginosa using in silico approaches.

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