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Envelope Glycoprotein based multi-epitope vaccine against a co-infection of Human Herpesvirus 5 and Human Herpesvirus 6 using in silico strategies.

ABSTRACT: The Human Betaherpesviruses HHV-5 and HHV-6 are quite inimical in immunocompromised hosts individually. A co-infection of both has been surmised to be far more disastrous. This can be attributed to a synergetic effect of their combined pathologies. While there have been attempts to develop a vaccine against each virus, no efforts were made to contrive an effective prophylaxis for the highly detrimental co-infection. In this study, an ensemble of viral envelope glycoproteins from both the viruses was utilized to design a multi-epitope vaccine using immunoinformatics tools. A collection of bacterial protein toll-like receptor agonists (BPTAs) was screened to identify a highly immunogenic adjuvant for the vaccine construct. The constructed vaccine was analysed using an array of methodologies ranging from World population coverage analysis to Immune simulation, whose results indicate high vaccine efficacy and stability. Furthermore, codon optimization and in silico cloning analysis were performed to check for efficient expression in a bacterial system. Collectively, these findings demonstrate the potential of the constructed vaccine to elicit an immune response against HHV-5 and HHV-6, thus supporting the viability of in vitro and in vivo studies.

SUBMITTER: Gandhamaneni BS

PROVIDER: S-EPMC9557995 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature

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Envelope Glycoprotein based multi-epitope vaccine against a co-infection of Human Herpesvirus 5 and Human Herpesvirus 6 using in silico strategies.

Gandhamaneni Bharath Sai BS Krishnamoorthy HemaNandini Rajendran HR Veerappapillai Shanthi S Mohapatra Soumya R SR Karuppasamy Ramanathan R

Glycoconjugate journal 20221013 6

The Human Betaherpesviruses HHV-5 and HHV-6 are quite inimical in immunocompromised hosts individually. A co-infection of both has been surmised to be far more disastrous. This can be attributed to a synergetic effect of their combined pathologies. While there have been attempts to develop a vaccine against each virus, no efforts were made to contrive an effective prophylaxis for the highly detrimental co-infection. In this study, an ensemble of viral envelope glycoproteins from both the viruses ...[more]

PMID: 36227524

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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:Human parechovirus (HPeV) is widely recognized as a severe viral infection affecting infants and neonates. Belonging to the Picornaviridae family, HPeV is categorized into 19 distinct genotypes. Among them, HPeV-1 is the most prevalent genotype, primarily associated with respiratory and digestive symptoms. Considering HPeV's role as a leading cause of life-threatening viral infections in infants and the lack of effective antiviral therapies, our focus centered on developing two multi-epitope vaccines, namely HPeV-Vax-1 and HPeV-Vax-2, using advanced immunoinformatic techniques. Multi-epitope vaccines have the advantage of protecting against various virus strains and may be preferable to live attenuated vaccines. Using the NCBI database, three viral protein sequences (VP0, VP1, and VP3) from six HPeV strains were collected to construct consensus protein sequences. Then the antigenicity, toxicity, allergenicity, and stability were analyzed after discovering T-cell and linear B-cell epitopes from the protein sequences. The fundamental structures of the vaccines were produced by fusing the selected epitopes with appropriate linkers and adjuvants. Comprehensive physicochemical, antigenic, allergic assays, and disulfide engineering demonstrated the effectiveness of the vaccines. Further refinement of secondary and tertiary models for both vaccines revealed promising interactions with toll-like receptor 4 (TLR4) in molecular docking, further confirmed by molecular dynamics simulation. In silico immunological modeling was employed to assess the vaccine's capacity to stimulate an immune reaction. In silico immunological simulations were employed to evaluate the vaccines' ability to trigger an immune response. Codon optimization and in silico cloning analyses showed that Escherichia coli (E. coli) was most likely the host for the candidate vaccines. Our findings suggest that these multi-epitope vaccines could be the potential HPeV vaccines and are recommended for further wet-lab investigation.

Dataset Information

Envelope Glycoprotein based multi-epitope vaccine against a co-infection of Human Herpesvirus 5 and Human Herpesvirus 6 using in silico strategies.

Publications

Envelope Glycoprotein based multi-epitope vaccine against a co-infection of Human Herpesvirus 5 and Human Herpesvirus 6 using in silico strategies.

Similar Datasets

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