Design of multi-epitope vaccine candidate based on OmpA, CarO and ZnuD proteins against multi-drug resistant Acinetobacter baumannii

Abstract

Acinetobacter baumannii has been identified as a major cause of nosocomial infections. Acinetobacter infections are often difficult to treat with multidrug resistant phenotypes. One of the most effective ways to combat infectious diseases is through vaccination. In this study, an attempt was made to select the most protective and potent immunostimulatory epitopes based on the epitope-rich domains of the ZnuD, OmpA and CarO proteins of Acinetobacter baumannii to design a vaccine that can protect against this infection. After predicting the epitope of B- and T-cells, seven antigenic regions of three proteins CarO, ZnuD and OmpA, were selected. These regions were bound by a GGGS linker. The binding affinity and molecular interactions of the vaccine with the immune receptors TLR2 and TLR4 were studied using molecular docking analysis. This vaccine design was subjected to in silico immune simulations using C-ImmSim. The designed vaccine was highly antigenic, non-allergenic and stable. TLR2 and TLR4 were selected to analyze the ability of the modeled chimeric protein to interact with immune system receptors. The results showed strong interaction between the designed protein vaccine with TLR2 (−18.8 kcal mol-1) and TLR4 (−15.1 kcal mol-1). To verify the stability of the interactions and the structure of the designed protein, molecular dynamics (MD) simulations were performed for 200 ns. Various analyses using MD showed that the protein structure is stable alone and in interaction with TLR2 and TLR4. The ability of the vaccine candidate protein to stimulate the immune system to produce the necessary cytokines and antibodies against Acinetobacter baumannii was also demonstrated by the ability of the protein designed using the C-ImmSim web server to induce an immune response. Therefore, the designed protein vaccine may be a suitable candidate for in vivo as well as in vitro studies against Acinetobacter baumannii infections.

Keywords

• Acinetobacter baumannii
• Epitope
• Vaccine
• Prediction
• Molecular dynamics