Protective Effect of DNA Vaccine Encoding Pseudomonas Exotoxin A and PcrV against Acute Pulmonary P. aeruginosa Infection

Abstract

Infections with Pseudomonas aeruginosa have been a long-standing challenge for clinical therapy because of complex pathogenesis and resistance to antibiotics, thus attaching importance to explore effective vaccines for prevention and treatment. In the present study, we constructed a novel DNA vaccine by inserting mutated gene toxAm encoding Pseudomonas Exotoxin A and gene pcrV encoding tip protein of the type III secretion system into respective sites of a eukaryotic plasmid pIRES, named pIRES-toxAm-pcrV, and next evaluated the efficacy of the vaccine in murine acute Pseudomonas pneumonia models. Compared to DNA vaccines encoding single antigen, mice vaccinated with pIRES-toxAm-pcrV elicited higher levels of antigen-specific serum immunoglobulin G (IgG), enhanced splenic cell proliferation and cytokine secretion in response to Pseudomonas aeruginosa antigens, additionally PAO1 challenge in mice airway resulted in reduced bacteria burden and milder pathologic changes in lungs. Besides, it was observed that immunogenicity and protection could be promoted by the CpG ODN 1826 adjuvant. Taken together, it’s revealed that recombinant DNA vaccine pIRES-toxAm-pcrV was a potential candidate for immunotherapy of Pseudomonas aeruginosa infection and the CpG ODN 1826 a potent stimulatory adjuvant for DNA vaccination.

Efficacy comparison of adjuvants in PcrV vaccine against Pseudomonas aeruginosa pneumonia

“…Although translocation inhibition of type III secretory toxins by anti‐PcrV antibodies has been suggested to be the main mechanism of the PcrV vaccine, activation of cellular immunity by CpG ODN could be helpful against P. aeruginosa . Previous studies have shown the effectiveness of CpG ODN as an adjuvant in a P. aeruginosa vaccine consisting of O‐polysaccharide from serotype IATS‐1 coupled with Toxin A , and in a DNA vaccine containing genes encoding Exotoxin A and PcrV . Moreover, in a Yersinia pestis vaccine study, a multiple antigen peptide synthesized from LcrV, a V antigen with homology to PcrV, was shown to be highly effective when combined with CpG ODN .…”

Pseudomonas Aeruginosa : Arsenal of Resistance Mechanisms, Decades of Changing Resistance Profiles, and Future Antimicrobial Therapies

“…Recent studies using adenovirus-based and DNA vaccine strategies incorporating different epitopes against P. aeruginosa have been considered attractive approaches that provide immunogenic and protective responses in animal models [186][187][188][189]. A recent study reported that antipseudmonal vaccines cannot be recommended in cystic fibrosis patients [190]; however, this cannot be generally concluded for other antipseudomonal vaccines in other infections in which further studies are required.…”

Association between Pseudomonas aeruginosa type III secretion, antibiotic resistance, and clinical outcome: a review

“…In prophylactic strategies, active immunization against PcrV ensures the survival of challenged mice and decreases lung inflammation and injury [ 89 ]. DNA vaccination with pIRES-toxAm-pcrV has been proposed as a potential immunotherapy [ 90 ]. In passive immunization, the rabbit polyclonal anti-PcrV antibody and murine monoclonal anti-PcrV antibody mAb166 inhibit TTS toxin translocation [ 91 - 95 ].…”