Immune responses and protective efficacy of a trivalent combination DNA vaccine based on oprL, oprF and flgE genes of Pseudomonas aeruginosa
download PDF

Pseudomonas aeruginosa is an infectious pathogenic bacteria infecting many different species of animals. Currently, it lacks a commercial vaccine. In this study, three monovalent DNA vaccines (poprL, poprF, and pflgE), three bivalent combination DNA vaccines (poprL+poprF, poprL+pflgE, poprF+pflgE), and a trivalent DNA vaccine (poprL+poprF+pflgE) were constructed. Consequently, we immunised chickens with these DNA vaccines and used inactivated vaccines as the positive controls. Then, the immune efficacy was evaluated through serum antibody detection, a lymphocyte proliferation assay, and cytokine concentration determination. Lastly, we assessed the protection rate through a challenge experiment. Following vaccination, the serum antibody levels induced using these DNA vaccines were different due to the different coating antigens. In the trivalent combination DNA vaccine group, we established that the lymphocyte proliferation (SI values), IFN-γ, IL-2, and IL-4 levels were significantly higher than those of the other six DNA vaccine groups and the inactivated vaccine group. However, the protection provided was slightly lower than that of the inactivated vaccine and higher than those of other DNA vaccines. The protection rate of poprL, poprF, pflgE, poprL+poprF, poprL+pflgE, poprF+pflgE, poprL+poprF+pflgE, and the inactivated vaccine were 50, 45, 60, 75, 80, 80, 90, and 95%, respectively. The results of this study indicated the trivalent DNA vaccine based on oprL, oprF and flgE genes represents a promising approach for the prevention of Pseudomonas aeruginosa infections.

Bahey-El-Din M, Mohamed SA, Sheweita SA, Haroun M, Zaghloul TI. 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. Int J Med Microbiol. 2020 Apr;310(3):151415.
Bumann D, Behre C, Behre K, Herz S, Gewecke B, Gessner JE, von Specht BU, Baumann U. Systemic, nasal and oral live vaccines against Pseudomonas aeruginosa: A clinical trial of immunogenicity in lower airways of human volunteers. Vaccine. 2010 Jan 8;28(3):707-13.
Doring G, Pier GB. Vaccines and immunotherapy against Pseudomonas aeruginosa. Vaccine. 2008 Feb 20;26(8):1011-24.
Fernandez-Esgueva M, Lopez-Calleja AI, Mulet X, Fraile-Ribot PA, Cabot G, Huarte R, Rezusta A, Oliver A. Characterization of AmpC β-lactamase mutations of extensively drug-resistant Pseudomonas aeruginosa isolates that develop resistance to ceftolozane/tazobactam during therapy. Enferm Infecc Microbiol Clin (Engl Ed). 2020 Dec;38(10):474-8.
Fournier C, Poirel L, Nordmann P. Implementation and evaluation of methods for the optimal detection of carbapenem-resistant and colistin-resistant Pseudomonas aeruginosa and Acinetobacter baumannii from stools. Diagn Microbiol Infect Dis. 2020 Oct;98(2):115121.
Gao C, Yang F, Wang Y, Liao Y, Zhang J, Zeng H, Zou Q, Gu J. Vaccination with a recombinant OprL fragment induces a Th17 response and confers serotype-independent protection against Pseudomonas aeruginosa infection in mice. Clin Immunol. 2017 Oct;183:354-63.
Gomi R, Sharma A, Wu W, Sung B, Worgall S. Post-exposure immunization by capsid-modified AdC7 vector expressing Pseudomonas aeruginosa OprF clears P. aeruginosa respiratory infection. Vaccine. 2017 Dec 18;35(51):7174-80.
Garvey MI, Bradley CW, Holden E, Weibren M. Where to do water testing for Pseudomonas aeruginosa in a healthcare setting. J Hosp Infect. 2017 Oct;97(2):192-5.
Gong Q, Ruan MD, Niu MF, Qin CL, Hou Y, Guo JZ. Immune efficacy of DNA vaccines based on oprL and oprF genes of Pseudomonas aeruginosa in chickens. Poult Sci. 2018a Dec 1;97(12):4219-27.
Gong Q, Kong LY, Niu MF, Qin CL, Yang Y, Li X, Ruan MD, Tian Y, Li ZL. Construction of a ptfA chitosan nanoparticle DNA vaccine against Pasteurella multocida and the immune response in chickens. Vet J. 2018b Jan;231:1-7.
Gong Q, Ruan M, Niu M, Qin C. Immune efficacy of different immunization doses of divalent combination DNA vaccine poprL+poprF of Pseudomonas aeruginosa. J Vet Med Sci. 2021 Dec 23;83(12):1959-64.
Hashemi FB, Behrouz B, Irajian G, Laghaei P, Korpi F, Fatemi MJ. A trivalent vaccine consisting of “flagellin A+B and pilin” protects against Pseudomonas aeruginosa infection in a murine burn model. Microb Pathog. 2020 Jan;138:103697.
Hashemizadeh Z, Mansouri S, Pahlavanzadeh F, Morones-Ramirez JR, Tabatabaeifar F, Motamedifar M, Gholizadeh A, Kalantar-Neyestanaki D. Evaluation of chromosomally and acquired mechanisms of resistance to carbapenem antibiotics among clinical isolates of Pseudomonas aeruginosa in Kerman, Iran. Gene Rep. 2020 Dec;21:100918.
Hassan R, El-Naggar W, Abd El-Aziz AM, Shaaban M, Kenawy HI, Ali YM. Immunization with outer membrane proteins (OprF and OprI) and flagellin B protects mice from pulmonary infection with mucoid and nonmucoid Pseudomonas aeruginosa. J Microbiol Immunol Infect. 2018 Jun;51(3):312-20.
Judd WR, Ratliff PD, Hickson RP, Stephens DM, Kennedy CA. Clinical and economic impact of meropenem resistance in Pseudomonas aeruginosa-infected patients. Am J Infect Control. 2016 Nov 1;44(11):1275-9.
Meynet E, Laurin D, Lenormand JL, Camara B, Toussaint B, Le Gouellec A. Killed but metabolically active Pseudomonas aeruginosa-based vaccine induces protective humoral- and cell-mediated immunity against Pseudomonas aeruginosa pulmonary infections. Vaccine. 2018 Mar 27;36(14):1893-900.
Mousavi M, Behrouz B, Irajian G, Mahdavi M, Korpi F, Motamedifar M. Passive immunization against Pseudomonas aeruginosa recombinant PilA in a murine burn wound model. Microb Pathog. 2016 Dec;101:83-8.
Pachori P, Gothalwal R, Gandhi P. Emergence of antibiotic resistance Pseudomonas aeruginosa in intensive care unit: A critical review. Genes Dis. 2019 Apr 17;6(2):109-19.
Ranjbar M, Behrouz B, Norouzi F, Mousavi Gargari SL. Anti-PcrV IgY antibodies protect against Pseudomonas aeruginosa infection in both acute pneumonia and burn wound models. Mol Immunol. 2019 Dec;116:98-105.
Rao YB, Ren ZX, Zhong JJ, Zhong XM, Cao B, Chen DM, Pan XN, Jia YP, Gao PM, Yang BY, Zhong Q, Yang J; Collaborative Study Group of Neonatal Hospital Infection Control. Risk factors for imipenem-resistant Pseudomonas aeruginosa in neonatal intensive care units in south China. J Hosp Infect. 2018 Mar;98(3):305-8.
Rashid MI, Naz A, Ali A, Andleeb S. Prediction of vaccine candidates against Pseudomonas aeruginosa: An integrated genomics and proteomics approach. Genomics. 2017 Jul;109(3-4):274-83.
Shariati A, Azimi T, Ardebili A, Chirani AS, Bahramian A, Pormohammad A, Sadredinamin M, Erfanimanesh S, Bostanghadiri N, Shams S, Hashemi A. Insertional inactivation of oprD in carbapenem-resistant Pseudomonas aeruginosa strains isolated from burn patients in Tehran, Iran. New Microbes New Infect. 2017 Dec 1;21:75-80.
Shebannavar S, Gade S, Nagappa K, Kotresh AM, Das SK. Comparative efficacy of oculonasal and intranasal routes of vaccination in induction of immune response against newcastle disease virus. Indian J Anim Res. 2010 Apr;44(4):270-4.
Staczek J, Gilleland LB, van der Heyde HC, Gilleland HE. DNA vaccines against chronic lung infections by Pseudomonas aeruginosa. FEMS Immunol Med Microbiol. 2003 Jul 15;37(2-3):147-53.
Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M, Monnet DL, Pulcini C, Kahlmeter G, Kluytmans J, Carmeli Y, Ouellette M, Outterson K, Patel J, Cavaleri M, Cox EM, Houchens CR, Grayson ML, Hansen P, Singh N, Theuretzbacher U, Magrini N; WHO Pathogens Priority List Working Group. Discovery, research, and development of new antibiotics: The WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis. 2018 Mar;18(3):318-27.
Wan C, Gao C, Xie Q, Wang Y, Cheng X, Fang Y, Liu Z, Zhang W, Zou Q, Lu G, Gu J. Flagella hook protein FlgE is a novel vaccine candidate of Pseudomonas aeruginosa identified by a genomic approach. Vaccine. 2021 Apr 22;39(17):2386-95.
Weimer ET, Ervin SE, Wozniak DJ, Mizel SB. Immunization of young African green monkeys with OprF epitope 8-OprI-type A- and B-flagellin fusion proteins promotes the production of protective antibodies against nonmucoid Pseudomonas aeruginosa. Vaccine. 2009 Nov 12;27(48):6762-9.
Xu Z, Xie J, Soteyome T, Peters BM, Shirtliff ME, Liu J, Harro JM. Polymicrobial interaction and biofilms between Staphylococcus aureus and Pseudomonas aeruginosa: An underestimated concern in food safety. Curr Opin Food Sci. 2019 Apr;26:57-64.
Yu X, Wang Y, Xia Y, Zhang L, Yang Q, Lei J. A DNA vaccine encoding VP22 of herpes simplex virus type I (HSV-1) and OprF confers enhanced protection from Pseudomonas aeruginosa in mice. Vaccine. 2016 Aug 17;34(37):4399-405.
Zuercher AW, Horn MP, Wu H, Song Z, Bundgaard CJ, Johansen HK, Hoiby N, Marcus P, Lang AB. Intranasal immunisation with conjugate vaccine protects mice from systemic and respiratory tract infection with Pseudomonas aeruginosa. Vaccine. 2006 May 15;24(20):4333-42.
download PDF

© 2022 Czech Academy of Agricultural Sciences | Prohlášení o přístupnosti