Abstract
Elizabethkingia meningoseptica is a ubiquitous Gram-negative emerging pathogen that causes hospital-acquired infection in both immunocompromised and immunocompetent patients. It is a multi-drug-resistant bacterium; therefore, an effective subunit immunogenic candidate is of great interest to encounter the pathogenesis of this pathogen. A protein-wide annotation of immunogenic targets was performed to fast-track the vaccine development against this pathogen, and structural-vaccinology-assisted epitopes were predicted. Among the total proteins, only three, A0A1T3FLU2, A0A1T3INK9, and A0A1V3U124, were shortlisted, which are the essential vaccine targets and were subjected to immune epitope mapping. The linkers EAAK, AAY, and GPGPG were used to link CTL, HTL, and B-cell epitopes and an adjuvant was also added at the N-terminal to design a multi-epitope immunogenic construct (MEIC). The computationally predicted physiochemical properties of the ensemble immunogen reported a highly antigenic nature and produced multiple interactions with immune receptors. In addition, the molecular dynamics simulation confirmed stable binding and good dynamic properties. Furthermore, the computationally modeled immune response proposed that the immunogen triggered a strong immune response after several doses at different intervals. Neutralization of the antigen was observed on the 3rd day of injection. Conclusively, the immunogenic construct produces protection against Elizabethkingia meningoseptica; however, further immunological testing is needed to unveil its real efficacy.
Highlights
Elizabethkingia meningoseptica, a Gram-negative, non-motile, rod-shaped saprophytic bacterium [1] is mostly distributed in soil, plants, water, frogs, foodstuffs, and fishes
To remove the recurrence of the same sequences in the same bacterial proteome, a list of non-homologous sequences was subjected to the CD-HIT server, using a 0.8 (80%) threshold [42]
The whole proteome of E. meningoseptica was retrieved from UniProt using the proteome ID (UP000188947) with a total of 3466 proteins, out of which the potential protein targets were prioritized to design a multi-epitope immunogenic construct (MEIC) against E. meningoseptica
Summary
Elizabethkingia meningoseptica, a Gram-negative, non-motile, rod-shaped saprophytic bacterium [1] is mostly distributed in soil, plants, water, frogs, foodstuffs, and fishes. It is a hospital-acquired pathogen reported in water sources, disinfectants, and medical instruments in hospitals and can be extracted from the sputum of patients with cystic fibrosis [2]. E. meningoseptica has the ability to evade the host immune system and spread to other parts of host tissues. It can circulate in the bloodstream of hosts and obtain nutrients from erythrocytes [3,4,5]. Premature neonates and low-weight infants weighing less than 2500 g are especially at risk, with 84% of these cases reported to have been caused by E. meningoseptica at a growing mortality rate of 52% [2,7,14,15]
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