Development of an mRNA vaccine against the OprF of Pseudomonas aeruginosa and evaluation of antibody response in mouse

Abstract

ABSTRACT Recently, antibiotic resistance has been recognized as a major threat to global public health. Pseudomonas aeruginosa (PA) is one of the most important opportunistic pathogens that mainly lead to dangerous nosocomial infections occurring in immunocompromised individuals. In recent years, with the increasing rate of multidrug resistance (MDR) of PA, management of infection with this pathogen has become a global challenge. Messenger RNA (mRNA) vaccines seem to be a good alternative to conventional vaccines. In the present study, an mRNA vaccine encoding OprF—outer membrane protein F—in PA was produced and synthesized using the in vitro transcription (IVT) method. Additionally, lipid nanoparticles (LNPs) were prepared by a thin-layer hydration method, and the prepared mRNA-LNP vaccine was evaluated in terms of nanoparticle properties. Finally, the efficacy of the vaccine in inducing a humoral immune response against PA was studied in BALB/c mice through injecting 5 or 25 μg of mRNA to each group. ELISA results showed an increase in the level of neutralizing antibodies against OprF protein in PA. Immunization with mRNA-OprF induced an appropriate humoral immune response and reduced bacterial burden in systemic infection models. It seems that the mRNA-OprF vaccine made in the present study can be a promising vaccine to prevent PA infection. IMPORTANCE This work is one of the suitable mRNA-LNP vaccine designs because it targets an important immunogenic antigen that can induce both humoral and adaptive immunity against bacteria. As the first project of mRNA vaccine, especially for a non-viral microorganism in Iran, our results demonstrate good humoral immunity Induced by the vaccine developed against P. aeruginosa. This work is of great importance and has significant potential to provide and develop an efficient vaccine against P. aeruginosa infections. This work is one of the suitable mRNA-LNP vaccine designs because it targets an important immunogenic antigen that can induce both humoral and adaptive immunity against bacteria. As the first project of mRNA vaccine, especially for a non-viral microorganism in Iran, our results demonstrate good humoral immunity Induced by the vaccine developed against P. aeruginosa. This work is of great importance and has significant potential to provide and develop an efficient vaccine against P. aeruginosa infections.