Abstract
Pseudomonas aeruginosa as a common pathogen causing urinary tract infections (UTIs) has been resistant to different antibiotics and developing an effective vaccine can be an alternative strategy. In the present study, the immunogenicity and protection efficacy of formulations composed of a hybrid protein composed of P. aeruginosa V-antigen (PcrV) and exoenzyme S (ExoS) with alum and MPL were evaluated. The hybrid protein could increase the specific systemic and mucosal immune responses, as well as cellular responses as compared with control groups. Combining of alum or MPL adjuvant with the hybrid protein significantly improved the levels of IgG1, serum IgA, mucosal IgG, and IL-17 as compared to the ExoS.PcrV alone. After bladder challenge with a P. aeruginosa strain, the bacterial loads of bladder and kidneys were significantly decreased in mice received ExoS.PcrV admixed with alum and ExoS.PcrV admixed with MPL than controls. The present study indicated that immunization of mice with a hybrid protein composed of ExoS and PcrV could induce multifactorial immune responses and opsonize the bacteria and decrease the viable bacterial cells. Because P. aeruginosa have caused therapeutic challenges worldwide, our study proposed ExoS.PcrV + alum and ExoS.PcrV + MPL as promising candidates for the prevention of infections caused by P. aeruginosa.
Highlights
Urinary tract infection (UTI) is a common community- and nosocomial-acquired infection in the world that infects approximately half of women and 12% of men in their lifetimes
Pseudomonas aeruginosa by natural or acquiring resistance to different classes of antibiotics become a major problem in the healthcare systems of the countries[4]
According to a report in 2017 in the United States, approximately 32,600 cases of Multi-drug resistance (MDR) P. aeruginosa infections was occurred in hospitalized patients that resulted in 2700 deaths and imposed approximately $757 million c osts[18]
Summary
Urinary tract infection (UTI) is a common community- and nosocomial-acquired infection in the world that infects approximately half of women and 12% of men in their lifetimes. A quarter of primary UTIs will result in recurrent infections between 6 and 12 months which antibiotic therapy of these infections is usually ineffective[1,2,3]. P. aeruginosa have acquired the versatility in different environments to cause different infections in men and women[5]. Susceptible humans especially those with immunocompromised immunity, burns, organ transplantation, and cystic fibrosis (CF) suffer more from infection with P. aeruginosa[6]. The effective way for treatment of UTI pathogens such as P. aeruginosa is antibiotics. Developing of a preventive vaccine can be an effective and cost-effective alternative to antibiotic therapy against UTI pathogens especially P. aeruginosa. Despite notable advancement in development of effective vaccines against P. aeruginosa, there is no approved vaccine as a universal vaccine for use in the world[4,9]
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