Evaluation of humoral immunity response to gold nanoparticles carrying Pseudomonas aeruginosa type IV pili in BALB/C mouse

Document Type : Research Paper

Authors

1 Department of Microbiology and Microbial Biotechnology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, Iran

2 Department of Basic Medical Sciences,, Khoy University of Medical Sciences, Khoy, Iran

3 Department of Nursing and Midwifery, Urmia University of Medical Sciences, Urmia, Iran

Abstract

Objective(s): Pseudomonas aeruginosa is one of the critical multidrug-resistant (MDR) pathogens. Vaccination could offer dual benefits by preventing sepsis caused by antimicrobial-resistant bacteria and curtailing the rise and selection of antimicrobial resistance due to excessive antibiotic use. With this in mind, we designed a vaccine candidate made of gold nanoparticles conjugated to pilin IV protein. Pilin IV protein is an important virulence factor in the pathogenesis of P. aeruginosa infections. 
Materials and Methods: Gold nanoparticles (AuNPs) were synthesized. The Gold nanoparticles were conjugated to the recombinant protein pilin IV. The recombinant protein pilin IV was emulsified in Montanide ISA 266’s adjuvant and was administered to BALB/c mice model via subcutaneous injection. The studied groups included recombinant protein with gold nanoparticles, recombinant protein with Montanide ISA 266’s adjuvant, and the control group. After blood sampling at the appropriate time points, ELISA test was performed on the serum of the mice groups. 
Resuls: The results showed that the two studied groups could stimulate the mouse’s immune system. Both IgG antibody subclasses were stimulated. 
Conclusion: This compound can be a new candidate for recombinant vaccine design against P. aeruginosa as a dexterous pathogen.

Keywords

References

1. Spagnolo AM, Sartini M, Cristina ML. Pseudomonas aeruginosa in the healthcare facility setting. Reviews and Research in Medical Microbiology. 2021; 32(3): 169-175.
2. Killough M, Rodgers AM, Ingram RJ. Pseudomonas aeruginosa: Recent advances in vaccine development. Vaccines. 2022; 10(7): 1100.
3. Dakterzada F, Mobarez AM, Roudkenar MH, Mohsenifar A. Induction of humoral immune response against Pseudomonas aeruginosa flagellin (1-161) using gold nanoparticles as an adjuvant. Vaccine. 2016; 34(12): 1472-1479. 
4. Bucior I, Pielage JF, Engel JN. Pseudomonas aeruginosa pili and flagella mediate distinct binding and signaling events at the apical and basolateral surface of airway epithelium. PLoS Pathog. 2012; 8(4): e1002616. 
5. Vartak A, Sucheck SJ. Recent Advances in Subunit Vaccine Carriers. Vaccines. 2016; 4(2):12. 
6. Apostólico Jde S, Lunardelli VA, Coirada FC, Boscardin SB, Rosa DS. Adjuvants: Classification, Modus Operandi, and Licensing. J Immunol Res. 2016; 2016: 1459394. 
7. Sekimukai H, Iwata‐Yoshikawa N, Fukushi S, Tani H, Kataoka M, Suzuki T, et al. Gold nanoparticle‐adjuvanted S protein induces a strong antigen‐specific IgG response against severe acute respiratory syndrome‐related coronavirus infection, but fails to induce protective antibodies and limit eosinophilic infiltration in lungs. Microbiol Immunol. 2020; 64(1): 33-51. 
8. Sengupta A, Azharuddin M, Al-Otaibi N, Hinkula J. Efficacy and immune response elicited by gold nanoparticle-based nanovaccines against infectious diseases. Vaccines. 2022; 10(4): 505. 
9. Frens, G. Controlled Nucleation for the Regulation of the Particle Size in Monodisperse Gold Suspensions. Nature physical science. 1973; 241(105): 20-22.
10. Krämer S, Xie H, Gaff J, Williamson JR, Tkachenko AG, Nouri N, et al. Preparation of protein gradients through the controlled deposition of protein-nanoparticle conjugates onto functionalized surfaces. J Am Chem Soc. 2004; 126(17):5388–5395.
11. Mashhadi Abolghasem Shirazi M,  Roohvand F, Arashkia A. Preparation and in vivo anti-tumor evaluation of human papillomavirus E7 adjuvanted with Montanide ISA 266 as a vaccine candidate. Vaccine Research. 2017; 4(1): 29-33.
12. Chirani AS, Majidzadeh R, Pouriran R, Heidary M, Nasiri MJ, Gholami M, et al. The effect of in silico targeting Pseudomonas aeruginosa patatin-like protein D, for immunogenic administration. Computational biology and chemistry. 2018; 74:12-19. 
13.El Solh AA, Alhajhusain A. Update on the treatment of Pseudomonas aeruginosa pneumonia. J Antimicrob Chemother. 2009; 64(2): 229-238.
14. Aloush V, Navon-Venezia S, Seigman-Igra Y, Cabili S, Carmeli Y. Multidrug-Resistant Pseudomonas aeruginosa: risk factors and clinical impact. Antimicrob Agents Chemother. 2006; 50(1): 43–48.
15. Tao W, Ziemer KS, Gill HS. Gold nanoparticle–M2e conjugate coformulated with CPG induces protective immunity against influenza virus. Nanomedicine. 2014; 9(2): 237–251.
16. Verma A, Arora SK, Kuravi SK, Ramphal R. Roles of specific amino acids in the N terminus of Pseudomonas aeruginosa flagellin and of flagellin glycosylation in the innate immune response. Infect Immun. 2005; 73(12): 8237–8246.
17. Didierlaurent A, Ferrero I, Otten LA, Dubois B, Reinhardt M, Carlsen H, et al. Flagellin promotes myeloid differentiation factor 88-dependent development of Th2-type response. J Immunol. 2004; 172(11): 6922–6930.
18. Campodónico VL, Llosa NJ, Grout M, Döring G, Maira-Litrán T, Pier GB. Evaluation of flagella and flagellin of Pseudomonas aeruginosa as vaccines. Infect Immun. 2010; 78(2): 746–755.
19.Petrovsky N, Aguilar JC. Vaccine adjuvants: current state and future trends. Immunol Cell Biol. 2004; 82: 488–496.
20.Staroverov SA, Ermilov DN, Shcherbakov AA, Semenov SV, Shchegolev SIu, Dykman LA. Generation of antibodies to Yersinia Pseudotuberculosis antigens using the colloid particles as an adjuvant. Zh Mikrobiol Epidemiol Immunobiol. 2003; 3: 54-57.
21.Vila A, Sánchez A, Janes K, Behrens I, Kissel T, Vila Jato JL, Alonso MJ, et al. Low molecular weight chitosan nanoparticles as new carriers for nasal vaccine delivery in mice. Eur J Pharm Biopharm. 2004; 57: 123–131.
22. Debache K, Kropf C, Schütz CA, Harwood LJ, Käuper P, Monney T, et al. Vaccination of mice with chitosan nanogel-associated recombinant NcPDI against challenge infection with Neospora caninum Tachyzoites. Parasite Immunol. 2011; 33: 81–94.
23. Ahmad Khan J, Pillai B, Kumar Das T, Singh Y, Maiti S. Molecular effects of uptake of gold nanoparticles in HeLa cells. Chem Bio Chem. 2007; 8: 1237-1240. 
24.Lasagna-Reeves C, Gonzalez-Romero D, Barria MA, Olmedo I, Clos A, Sadagopa Ramanujam VM, et al. Bioaccumulation and toxicity of gold nanoparticles after repeated administration in mice. Biochem Biophys Res Commun. 2010; 393: 649–655.
25.Holder IA, Wheeler R, Montie TC. Flagellar preparations from Pseudomonas aeruginosa: animal protection studies. Infect Immun. 1982; 35: 276-280. 
26. Holder IA, Naglich JG. Experimental studies of the pathogenesis of infections due to Pseudomonas aeruginosa: immunization using divalent flagella preparations. J Trauma. 1986; 26(2): 118-122.
27. Bastús NG, Sánchez-Tilló E, Pujals S, farrera C, Kogan MJ, Giralt E, et al. Peptides conjugated to gold nanoparticles induce macrophage activation. Mol Immunol. 2009; 46(4): 743–748.
Nanomedicine Journal
Volume 11, Issue 1
January 2024
Pages 44-51

Files

Share

How to cite

Statistics