Recombinant N-terminal outer membrane porin (OprF) of Pseudomonas aeruginosa is a promising vaccine candidate against both P. aeruginosa and some strains of Acinetobacter baumannii

Abstract

Pseudomonas aeruginosa is an evolving pathogen which can cause serious infections especially to immunocompromised patients. Its high resistance profile to antibiotics results in difficulty, and sometimes impossibility, in treating afflicted patients. Developing an effective vaccine against P. aeruginosa is an important approach to tackle this problem. A similar problematic situation exists for Acinetobacter baumannii. Several vaccine candidates have been investigated up till now but still there is no approved vaccine in the market. One important antigen of P. aeruginosa is the outer membrane protein F (OprF) which functions as a porin with relevant important roles in virulence. Previous studies focused mainly on the C-terminal peptidoglycan binding domain of OprF as a vaccine candidate. In the current study, we have investigated the N-terminal porin domain of OprF as a potential vaccine candidate against P. aeruginosa. Histidine-tagged recombinant N-terminal OprF (amino acid range 25-200; OprF_25-200) was overexpressed in Escherichia coli and purified using metal affinity chromatography. Swiss albino mice were immunized with OprF_25-200 adjuvanted with Bacillus Calmette-Guérin (BCG) and alum and the immune response was evaluated. Immunized mice developed antigen-specific IgG1 and IgG2a and were protected against challenge by both P. aeruginosa and a clinical isolate of A. baumannii expressing OprF. Serum from OprF_25-200-immunized mice showed cross-reactivity with both pathogens using western blotting and whole cell enzyme-linked immunosorbent assay (ELISA). To our knowledge, this is the first report to demonstrate that the N-terminal domain of OprF is sufficiently immunogenic to protect against the two pathogens.

Keywords: Acinetobacter baumannii; N-terminal domain; OprF; Outer membrane porin F; Pseudomonas aeruginosa; Vaccine.