Proteome-Wide Mapping and Reverse Vaccinology Approaches to Design a Multi-Epitope Vaccine against Clostridium perfringens

Abstract

C. perfringens is a highly versatile bacteria of livestock and humans, causing enteritis (a common food-borne illness in humans), enterotoxaemia (in which toxins are formed in the intestine which damage and destroy organs, i.e., the brain), and gangrene (wound infection). There is no particular cure for the toxins of C. perfringens. Supportive care (medical control of pain, intravenous fluids) is the standard treatment. Therefore, a multiple-epitope vaccine (MEV) should be designed to battle against C. perfringens infection. Furthermore, the main objective of this in silico investigation is to design an MEV that targets C. perfringens. For this purpose, we selected the top three proteins that were highly antigenic using immuno-informatics approaches, including molecular docking. B-cells, IFN-gamma, and T cells for target proteins were predicted and the most conserved epitopes were selected for further investigation. For the development of the final MEV, epitopes of LBL5, CTL17, and HTL13 were linked to GPGPG, AAY, and KK linkers. The vaccine N-end was joined to an adjuvant through an EAAK linker to improve immunogenicity. After the attachment of linkers and adjuvants, the final construct was 415 amino acids. B-cell and IFN-gamma epitopes demonstrate that the model structure is enhanced for humoral and cellular immune responses. To validate the immunogenicity and safety of the final construct, various physicochemical properties, and other properties such as antigenicity and non-allergens, were evaluated. Furthermore, molecular docking was carried out for verification of vaccine compatibility with the receptor, evaluated in silico. Also, in silico cloning was employed for the verification of the proper expression and credibility of the construct.

Genome-Based Multi-Antigenic Epitopes Vaccine Construct Designing against Staphylococcus hominis Using Reverse Vaccinology and Biophysical Approaches

“…This adjuvant molecule was linked with the epitopes constructed with the help of the EAAK linker. The cholera toxin B subunit adjuvant was used in the process [ 70 ]. The 3D structure of the construct was modeled using the 3Dpro program of Scratch protein predictor.…”

“…Computational vaccine designing strategies are exponentially growing, mainly because of the huge growth of genomic data that has allowed scientists to move beyond Pasteur’s rule of vaccinology and instead use computational approaches, tools, and software to design vaccines without the need for any wet-lab techniques. A previous study conducted by Aldakheel et al designed an MEV using proteome-wide mapping and reverse vaccinology and used the same computational framework to model highly antigenic and potent MEV targets against Clostridium perfringens [ 70 ]. The same computational approach was used by Al-Megrin et al They designed a novel MEV against Staphylococcus auricularis using immunoinformatics and biophysics approaches.…”

Immunoinformatic analysis of the whole proteome for vaccine design: An application to Clostridium perfringens

“…Our construct of 150 aa is made of 9 overlapped HTL-CTL epitopes, comprising 24 HTL-epitopes containing 34 CTLepitopes. This suggests a better cellular immune response than previous multiepitope constructs, which were longer and had less epitopes in its sequence (114). Whilst the study of Aldakheel et al (114) attempted to target all HLA-I and -II alleles, we opted to focus on the HLA supertype alleles.…”

“…This suggests a better cellular immune response than previous multiepitope constructs, which were longer and had less epitopes in its sequence (114). Whilst the study of Aldakheel et al (114) attempted to target all HLA-I and -II alleles, we opted to focus on the HLA supertype alleles. This allowed us to need less epitopes in our design to match all the target alleles.…”

Development of a Candidate Multi-Epitope Subunit Vaccine against Klebsiella aerogenes: Subtractive Proteomics and Immuno-Informatics Approach

“…Antigenic protein fragments that can duplicate the actions of the current pathogen and elicit an immune response to the pathogen might be supported by vaccine components [10]. Antigenic protein fragments in the vaccine's subunits can copy the real pathogen and activate an immune response against the targeted bacteria [17][18][19][20][21][22][23][24]. We anticipate that the findings of this report will construct a new candidate vaccine for K. aerogenes.…”