Design and in silico analysis of mRNA vaccine construct against Salmonella

Abstract

Salmonella infections are continuously growing. Causative serovars have gained enhanced drug resistance and virulence. Current vaccines have fallen short of providing sufficient protection. mRNA vaccines have come up with huge success against SARS-CoV-2; Pfizer-BioNTech and Moderna vaccines have resulted in >90% efficacy with efficient translocation, expression, and presentation of antigen to the host immune system. Herein, based on the same approach a mRNA vaccine construct has been designed and analyzed against Salmonella by joining regions of genes of outer membrane proteins C and F of S. Typhi through a flexible linker. Construct was flanked by regulatory regions that have previously shown better expression and translocation of encoded protein. GC content of the construct was improved to attain structural and thermodynamic stability and smooth translation. Sites of strong binding miRNAs were removed through codon optimization. Protein encoded by this construct is structurally plausible, highly antigenic, non-allergen to humans, and does not cross-react to the human proteome. It is enriched in potent, highly antigenic, and conserved linear and conformational epitopes. Most conserved conformational epitopes of core protein lie on extended beta hairpins exposed to the cellular exterior. Stability and thermodynamic attributes of the final construct were found highly comparable to the Pfizer-BioNTech vaccine construct. Both contain a stable stem-loop structure downstream of the start codon and do not offer destabilizing secondary structures upstream of the start codon. Given structural and thermodynamic stability, effective immune response, and epitope composition the construct is expected to provide broad-spectrum protection against clinically important Salmonella serovars.

Communicated by Ramaswamy H. Sarma

Keywords:

• mRNA vaccine
• Salmonella serovars
• multivariant
• OmpC
• OmpF

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

Institutional review board statement

Not applicable.

Informed consent statement

Not applicable.

Author contributions

Conceptualization, Muhammad Janees Imdad; Methodology, Muhammad Janees Imdad, Muhammad Naseem Khan, Hafiz Shahood Alam, Adnan Khan and Faraz Ahmed; Project administration, Adnan Khan and Muhammad Naseem Khan; Data acquisition, Muhammad Janees Imdad, Muhammad Naseem Khan, Adnan Khan, Abdul Basit Khan and Zulfiqar Ali Mirani; Writing – original draft, Muhammad Janees Imdad, Muhammad Naseem Khan, Adnan Khan and Hafiz Shahood Alam; Writing – review & editing, Muhammad Janees Imdad, Muhammad Naseem Khan, Adnan Khan, Abdul Basit Khan, Zulfiqar Ali Mirani and Faraz Ahmed.