Immunoinformatics Design of Multiepitope Vaccine Against Enterococcus faecium Infection

• Published in: International journal of peptide research and therapeutics Vol. 27; no. 4; pp. 2183 - 2198
• Main Authors: Fatoba, Abiodun J., Adeleke, Victoria T., Maharaj, Leah, Okpeku, Moses, Adeniyi, Adebayo A., Adeleke, Matthew A.
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01-12-2021; Springer Nature B.V
• Subjects: Animal Anatomy; Antibiotic resistance; Antibiotics; Antigens; Biochemistry; Bioinformatics; Biomedical and Life Sciences; CD4 antigen; CD8 antigen; Drb1 protein; Enterococcus faecium; Epitopes; Histocompatibility antigen HLA; Histology; Hospitals; Infections; Life Sciences; Lymphocytes T; Molecular Medicine; Morphology; Pathogens; Pharmaceutical Sciences/Technology; Pharmacology/Toxicology; Polymer Sciences; TLR2 protein; Toll-like receptors; Vaccination; Vaccines; γ-Interferon; Infection; Secreted antigen A (SagA); Immune-response; Multiepitope; Peptidyl-prolyl cis–trans isomerase (PPic); Immunoinformatics
• ISSN: 1573-3149; 1573-3904
• DOI: 10.1007/s10989-021-10245-5

Enterococcus faecium
has emerged as the fourth most commonly isolated nosocomial pathogen due to its resistance to commonly used antibiotics and, as such, poses a serious threat to human health. Alternative control through vaccination has received much attention, but there is no clinically approved vaccine against this pathogen. This, therefore, necessitates the need for a novel vaccine design. This present study was conducted to design a multiepitope-based vaccine (MEV) against
E. faecium
infection based on the secreted antigen A (SagA) and peptidyl-prolyl cis–trans isomerase (PPic) of this pathogen which are promising vaccine candidates. A final total of 7 CD8
+
T-cell and 11 CD4
+
T-cell epitopes, which are highly antigenic, IFN-γ inducer, and overlapping, were shortlisted from both protein antigens. The selected epitopes showed good population coverage and interacted with both HLA-A*02:06 and HLA-DRB1*01:01 alleles. The constructed MEV which consists of T-cell epitopes of both SagA and PPic antigen was fused by linkers and adjuvant. The 3D structure of the MEV construct was predicted, refined, and validated using different bioinformatics tools. The MEV construct showed a strong binding interaction and stability with Toll-like receptor 2 (TLR2). Finally, the vaccine construct was codon-optimised for expression in
E. coli
K12 system and cloned into a pET-28a (+) vector. This study provides background for designing a suitable, safe, and effective vaccine against antibiotic-resistant
E. faecium
infection.