Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
권호 표지
DOI QR코드

DOI QR Code

Increased Immunogenicity and Protective Efficacy of a P. aeruginosa Vaccine in Mice Using an Alum and De-O-Acylated Lipooligosaccharide Adjuvant System

  • Ryu, Ji In (Department of Bioscience and Biotechnology, Sejong University) ;
  • Wui, Seo Ri (Department of Bioscience and Biotechnology, Sejong University) ;
  • Ko, Ara (Department of Bioscience and Biotechnology, Sejong University) ;
  • Do, Hien Thi Thu (Department of Bioscience and Biotechnology, Sejong University) ;
  • Lee, Yeon Jeong (Department of Bioscience and Biotechnology, Sejong University) ;
  • Kim, Hark Jun (Department of Bioscience and Biotechnology, Sejong University) ;
  • Rhee, Inmoo (Department of Bioscience and Biotechnology, Sejong University) ;
  • Park, Shin Ae (R & D Center, EyeGene) ;
  • Kim, Kwang Sung (R & D Center, EyeGene) ;
  • Cho, Yang Je (R & D Center, EyeGene) ;
  • Lee, Na Gyong (Department of Bioscience and Biotechnology, Sejong University)
  • Received : 2017.06.05
  • Accepted : 2017.06.13
  • Published : 2017.08.28
Download PDF
⟨ Previous Next ⟩

Abstract

Pseudomonas aeruginosa (P. aeruginosa) is an opportunistic pathogen that commonly causes fatal infections in cystic fibrosis and burn patients as well as in patients who are hospitalized or have impaired immune systems. P. aeruginosa infections are difficult to treat owing to the high resistance of the pathogen to conventional antibiotics. Despite several efforts, no effective prophylactic vaccines against P. aeruginosa are currently available. In this study, we investigated the activity of the CIA06 adjuvant system, which is composed of alum and de-O-acylated lipooligosaccharide, on a P. aeruginosa outer membrane protein (OMP) antigen vaccine in mice. The results indicated that CIA06 significantly increased the antigen-specific IgG titers and opsonophagocytic activity of immune sera against P. aeruginosa. In addition, the antibodies induced by the CIA06-adjuvanted vaccine exhibited higher cross-reactivity with heterologous P. aeruginosa strains. Finally, mice immunized with the CIA06-adjuvanted vaccine were effectively protected from lethal P. aeruginosa challenge. Based on these data, we suggest that the CIA06 adjuvant system might be used to promote the immunogenicity and protective efficacy of the P. aeruginosa OMP vaccine.

Keywords

References

  1. Duraisingham SS, Hanson S, Buckland M, Grigoriadou S, Longhurst HJ. 2014. Pseudomonas infection in antibody deficient patients. Eur. J. Microbiol. Immunol. 4: 198-203. https://doi.org/10.1556/EUJMI-D-14-00026
  2. Vincent JL, Rello J, Marshall J, Silva E, Anzueto A, Martin CD, et al. 2009. International study of the prevalence and outcomes of infection in intensive care units. JAMA 302: 2323-2329. https://doi.org/10.1001/jama.2009.1754
  3. Gibson RL, Burns JL, Ramsey BW. 2003. Pathophysiology and management of pulmonary infections in cystic fibrosis. Am. J. Respir. Crit. Care Med. 168: 918-951. https://doi.org/10.1164/rccm.200304-505SO
  4. Kang CI, K im SH, K im HB, Park SW, Choe Y J, O h MD, et al. 2003. Pseudomonas aeruginosa bacteremia: risk factors for mortality and influence of delayed receipt of effective antimicrobial therapy on clinical outcome. Clin. Infect. Dis. 37: 745-751. https://doi.org/10.1086/377200
  5. Richards MJ, Edwards JR, Culver DH, Gaynes RP. 2000. Nosocomial infections in combined medical-surgical intensive care units in the United States. Infect. Control Hosp. Epidemiol. 21: 510-515. https://doi.org/10.1086/501795
  6. Centers for Disease Control and Prevention. 2013. Antibiotic resistance threats in the United States. Available from http://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf.
  7. Macvane SH. 2017. Antimicrobial resistance in the intensive care unit: a focus on gram-negative bacterial infections. J. Intensive Care Med. 32: 25-37. https://doi.org/10.1177/0885066615619895
  8. Vincent JL. 2014. Vaccine development and passive immunization for Pseudomonas aeruginosa in critically ill patients: a clinical update. Future Microbiol. 9: 457-463. https://doi.org/10.2217/fmb.14.10
  9. Priebe GP, Goldberg JB. 2014. Vaccines for Pseudomonas aeruginosa: a long and w inding road. Expert Rev. Vaccines 13: 507-519. https://doi.org/10.1586/14760584.2014.890053
  10. Alexander JW, Fisher MW, MacMillan BG. 1971. Immunological control of Pseudomonas infection in burn patients: a clinical evaluation. Arch. Surg. 102: 31-35. https://doi.org/10.1001/archsurg.1971.01350010033008
  11. Young LS, Meyer RD, Armstrong D. 1973. Pseudomonas aeruginosa vaccine in cancer patients. Ann. Intern. Med. 79: 518-527. https://doi.org/10.7326/0003-4819-79-4-518
  12. DiGiandomenico A, Rao J, Harcher K, Zaidi TS, Gardner J, Neely AN, et al. 2007. Intranasal immunization with heterologously expressed polysaccharide protects against multiple Pseudomonas aeruginosa infections. Proc. Natl. Acad. Sci. USA 104: 4624-4629. https://doi.org/10.1073/pnas.0608657104
  13. Bridge DR, Whitmire JM, Makobongo MO, Merrell DS. 2016. Heterologous Pseudomonas aeruginosa O-antigen delivery using a Salmonella enterica serovar Typhimurium wecA mutant strain. Int. J. Med. Microbiol. 306: 529-540. https://doi.org/10.1016/j.ijmm.2016.06.005
  14. Rello J, Krenn CG, Locker G, Pilger E, Madl C, Balica L, et al. 2017. A randomized placebo-controlled phase II study of a Pseudomonas vaccine in ventilated ICU patients. Crit. Care 21: 22. https://doi.org/10.1186/s13054-017-1601-9
  15. Hassan R, El-Naggar W, Abd El-Aziz AM, Shaaban M, Kenawy HI, Ali YM. 2017. 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. DOI: 10.1016/j.jmii.2016.08.014.
  16. Kim DK, Kim JJ, Kim JH, Woo YM, Kim S, Yoon DW, et al. 2000. Comparison of two immunization schedules for a Pseudomonas aeruginosa outer membrane proteins vaccine in burn patients. Vaccine 19: 1274-1283. https://doi.org/10.1016/S0264-410X(00)00235-8
  17. Li H, Mo KF, Wang Q, Stover CK, DiGiandomenico A, Boons GJ. 2013. Epitope mapping of monoclonal antibodies using synthetic oligosaccharides uncovers novel aspects of immune recognition of the Psl exopolysaccharide of Pseudomonas aeruginosa. Chemistry 19: 17425-17431. https://doi.org/10.1002/chem.201302916
  18. Thaden JT, Keller AE, Shire NJ, Camara MM, Otterson L, Huband M, et al. 2016. Pseudomonas aeruginosa bacteremic patients exhibit nonprotective antibody titers against therapeutic antibody targets PcrV and Psl exopolysaccharide. J. Infect. Dis. 213: 640-648. https://doi.org/10.1093/infdis/jiv436
  19. Sawa T, Ito E, Nguyen VH, Haight M. 2014. Anti-PcrV antibody strategies against virulent Pseudomonas aeruginosa. Hum. Vaccin. Immunother. 10: 2843-2852. https://doi.org/10.4161/21645515.2014.971641
  20. Hamaoka S, Naito Y, Katoh H, Shimizu M, Kinoshita M, Akiyama K. 2017. Efficacy comparison of adjuvants in PcrV vaccine against Pseudomonas aeruginosa pneumonia. Microbiol. Immunol. 61: 64-74. https://doi.org/10.1111/1348-0421.12467
  21. Campodonico VL, Llosa NJ, Bentancor LV, Maira-Litran T, Pier GB. 2011. Efficacy of a conjugate vaccine containing polymannuronic acid and flagellin against experimental Pseudomonas aeruginosa lung infection in mice. Infect. Immun. 79: 3455-3464. https://doi.org/10.1128/IAI.00157-11
  22. Dakterzada F, Mohabati Mobarez A, Habibi Roudkenar M, Mohsenifar A. 2016. Induction of humoral immune response against Pseudomonas aeruginosa flagellin (1-161) using gold nanoparticles as an adjuvant. Vaccine 34: 1472-1479. https://doi.org/10.1016/j.vaccine.2016.01.041
  23. Saffari M, Behbood S, Irajian G, Khorshidi A, Moniri R, Behrouz B. 2017. Antibodies raised against divalent type b flagellin and pilin provide effective immunotherapy against Pseudomonas aeruginosa infection of mice with burn wounds. Biologicals 45: 20-26. https://doi.org/10.1016/j.biologicals.2016.10.007
  24. Banadkoki AZ, Keshavarzmehr M, Afshar Z, Aleyasin N, Fatemi MJ, Behrouz B, et al. 2016. Protective effect of pilin protein with alum+naloxone adjuvant against acute pulmonary Pseudomonas aeruginosa infection. Biologicals 44: 367-373. https://doi.org/10.1016/j.biologicals.2016.06.009
  25. Haghbin M, Armstrong D, Murphy ML. 1973. Controlled prospective trial of Pseudomonas aeruginosa vaccine in children with acute leukemia. Cancer 32: 761-766. https://doi.org/10.1002/1097-0142(197310)32:4<761::AID-CNCR2820320405>3.0.CO;2-H
  26. Lam MY, McGroarty EJ, Kropinski AM, MacDonald LA, Pedersen SS, Hoiby N, et al. 1989. Occurrence of a common lipopolysaccharide antigen in standard and clinical strains of Pseudomonas aeruginosa. J. Clin. Microbiol. 27: 962-967.
  27. Mutharia LM, Nicas TI, Hancock RE. 1982. Outer membrane proteins of Pseudomonas aeruginosa serotype strains. J. Infect. Dis. 146: 770-779. https://doi.org/10.1093/infdis/146.6.770
  28. Kim YG, Kim JH, Park WH, Ahn DH, Hong KH, Kim HS, et al. 1994. Protective effect of CFC-101, a Pseudomonas vaccine, in mice. J. Appl. Pharmacol. 2: 322-325.
  29. Park WJ, Cho YJ, Ahn DH, Jung SB, Lee NG, Kim HS, et al. 1997. An outer membrane protein preparation as a vaccine against Pseudomonas aeruginosa infection. J. Microbiol. Biotechnol. 7: 144-150.
  30. Jang IJ, Kim IS, Park WJ, Yoo KS, Yim DS, Kim HK, et al. 1999. Human immune response to a Pseudomonas aeruginosa outer membrane protein vaccine. Vaccine 17: 158-168. https://doi.org/10.1016/S0264-410X(98)00159-5
  31. Lee NG, Jung SB, Ahn BY, Kim YH, Kim JJ, Kim DK, et al. 2000. Immunization of burn-patients with a Pseudomonas aeruginosa outer membrane protein vaccine elicits antibodies with protective efficacy. Vaccine 18: 1952-1961. https://doi.org/10.1016/S0264-410X(99)00479-X
  32. Lee NG, Ahn BY, Jung SB, Kim YG, Lee Y, Kim HS, et al. 1999. Human anti-Pseudomonas aeruginosa outer membrane proteins IgG cross-protective against infection with heterologous immunotype strains of P. aeruginosa. FEMS Immunol. Med. Microbiol. 25: 339-347.
  33. Doring G, Meisner C, Stern M. 2007. A double-blind randomized placebo-controlled phase III study of a Pseudomonas aeruginosa flagella vaccine in cystic fibrosis patients. Proc. Natl. Acad. Sci. USA 104: 11020-11025. https://doi.org/10.1073/pnas.0702403104
  34. Cho YJ, Ahn BY, Lee NG, Lee DH, Kim DS. 2006. A combination of E. coli DNA fragments and modified lipopolysaccharides as a cancer immunotherapy. Vaccine 24: 5862-5871. https://doi.org/10.1016/j.vaccine.2006.04.048
  35. Han JE, Wui SR, Kim KS, Cho YJ, Cho WJ, Lee NG. 2014. Characterization of the structure and immunostimulatory activity of a vaccine adjuvant, de-O-acylated lipooligosaccharide. PLoS One 9: e85838. https://doi.org/10.1371/journal.pone.0085838
  36. Han JE, Kim HK, Park SA, Lee SJ, Kim HJ, Son GH, et al. 2010. A nontoxic derivative of lipopolysaccharide increases immune responses to Gardasil HPV vaccine in mice. Int. Immunopharmacol. 10: 169-176. https://doi.org/10.1016/j.intimp.2009.10.012
  37. Han JE, Wui SR, Park SA, Lee NG, Kim KS, Cho YJ, et al. 2012. Comparison of the immune responses to the CIA06-adjuvanted human papillomavirus L1 VLP vaccine with those against the licensed HPV vaccine Cervarix TM in mice. Vaccine 30: 4127-4134. https://doi.org/10.1016/j.vaccine.2012.04.079
  38. Wui SR, Kim HK, Han JE, Kim JM, Kim YH, Chun JH, et al. 2011. A combination of the TLR4 agonist CIA05 and alum promotes the immune responses to Bacillus anthracis protective antigen in mice. Int. Immunopharmacol. 11: 1195-1204. https://doi.org/10.1016/j.intimp.2011.03.020
  39. Wui SR, Han JE, Kim YH, Rhie GE, Lee NG. 2013. Increased long-term immunity to Bacillus anthracis protective antigen in mice immunized with a CIA06B-adjuvanted anthrax vaccine. Arch. Pharm. Res. 36: 464-471. https://doi.org/10.1007/s12272-013-0034-5
  40. Ryu JI, Park SA, Wui SR, Ko A, Han JE, Choi JA, et al. 2016. A de-O-acylated lipooligosaccharide-based adjuvant system promotes antibody and Th1-type immune responses to H1N1 pandemic influenza vaccine in mice. Biomed. Res. Int. 2016: 3713656.
  41. Inoue K, Hamana Y, Mitsuhashi S. 1995. In vitro antibacterial activity and beta-lactamase stability of a new carbapenem, BO-2727. Antimicrob. Agents Chemother. 39: 2331-2336. https://doi.org/10.1128/AAC.39.10.2331
  42. Raymond CK, Sims EH, Kas A, Spencer DH, Kutyavin TV, Ivey RG, et al. 2002. Genetic variation at the O-antigen biosynthetic locus in Pseudomonas aeruginosa. J. Bacteriol. 184: 3614-3622. https://doi.org/10.1128/JB.184.13.3614-3622.2002
  43. Lee CH, Tsai CM. 1999. Quantification of bacterial lipopolysaccharides by the purpald assay: measuring formaldehyde generated from 2-keto-3-deoxyoctonate and heptose at the inner core by periodate oxidation. Anal. Biochem. 267: 161-168. https://doi.org/10.1006/abio.1998.2961
  44. Zuercher AW, Horn M P, W u H, S ong Z, Bundg aard C J, Johansen HK, et al. 2006. Intranasal immunisation with conjugate vaccine protects mice from systemic and respiratory tract infection with Pseudomonas aeruginosa. Vaccine 24: 4333-4342. https://doi.org/10.1016/j.vaccine.2006.03.007
  45. Fabbrini M, Sammicheli C, Margarit I, Maione D, Grandi G, Giuliani MM, et al. 2012. A new flow-cytometry-based opsonophagocytosis assay for the rapid measurement of functional antibody levels against Group B Streptococcus. J. Immunol. Methods 378: 11-19. https://doi.org/10.1016/j.jim.2012.01.011
  46. Mutharia LM, Nicas TI, Hancock RE. 1982. Outer membrane proteins of Pseudomonas aeruginosa serotype strains. J. Infect. Dis. 146: 770-779. https://doi.org/10.1093/infdis/146.6.770
  47. Ramos HC, Rumbo M, Sirard JC. 2004. Bacterial flagellins: mediators of pathogenicity and host immune responses in mucosa. Trends Microbiol. 12: 509-517. https://doi.org/10.1016/j.tim.2004.09.002
  48. Feltman H, Schulert G, Khan S, Jain M, Peterson L, Hauser AR. 2001. Prevalence of type III secretion genes in clinical and environmental isolates of Pseudomonas aeruginosa. Microbiology 147: 2659-2669. https://doi.org/10.1099/00221287-147-10-2659
  49. Priebe GP, Walsh RL, Cederroth TA, Kamei A, Coutinho-Sledge YS, Goldberg JB, et al. 2008. IL-17 is a critical component of vaccine-induced protection against lung infection by lipopolysaccharide-heterologous strains of Pseudomonas aeruginosa. J. Immunol. 181: 4965-4975. https://doi.org/10.4049/jimmunol.181.7.4965
  50. Bayes HK, Ritchie ND, Evans TJ. 2016. Interleukin-17 is required for control of chronic lung infection caused by Pseudomonas aeruginosa. Infect. Immun. 84: 3507-3516. https://doi.org/10.1128/IAI.00717-16
  51. Pan T, Tan R, Li M, Liu Z, Wang X, Tian L, et al. 2016. IL17-producing ${\gamma}$${\delta}$ T cells may enhance humoral immunity during pulmonary Pseudomonas aeruginosa infection in mice. Front. Cell. Infect. Microbiol. 6: 170.
  52. Korn T, Bettelli E, Oukka M, Kuchroo VK. 2009. IL-17 and Th17 cells. Annu. Rev. Immunol. 27: 485-517. https://doi.org/10.1146/annurev.immunol.021908.132710
  53. Ouyang W, Kolls JK, Zheng Y. 2008. The biological functions of T helper 17 cell effector cytokines in inflammation. Immunity 28: 454-467. https://doi.org/10.1016/j.immuni.2008.03.004
  54. Rendon JL, Choudhry MA. 2012. Th17 cells: critical mediators of host responses to burn injury and sepsis. J. Leukoc. Biol. 92: 529-538. https://doi.org/10.1189/jlb.0212083
  55. Neely CJ, Maile R, Wang MJ, Vadlamudi S, Meyer AA, Cairns BA. 2011. Th17 (IFN${\gamma}$-IL17+) CD4+ T cells generated after burn injury may be a novel cellular mechanism for postburn immunosuppression. J. Trauma 70: 681-690. https://doi.org/10.1097/TA.0b013e31820d18a6
  56. Wu W, Huang J, Duan B, Traficante DC, Hong H, Risech M, et al. 2012. Th17-stimulating protein vaccines confer protection against Pseudomonas aeruginosa pneumonia. Am. J. Respir. Crit. Care Med. 186: 420-427. https://doi.org/10.1164/rccm.201202-0182OC
  57. Kamei A, Wu W, Traficante DC, Koh AY, Van Rooijen N, Pier GB, et al. 2013. Collaboration between macrophages and vaccine-induced CD4+ T cells confers protection against lethal Pseudomonas aeruginosa pneumonia during neutropenia. J. Infect. Dis. 207: 39-49. https://doi.org/10.1093/infdis/jis657
  58. Mitsdoerffer M, Lee Y, Jager A, Kim HJ, Korn T, Kolls JK, et al. 2010. Proinflammatory T helper type 17 cells are effective B-cell helpers. Proc. Natl. Acad. Sci. USA 107: 14292-14297. https://doi.org/10.1073/pnas.1009234107

Cited by

  1. Comparison of the adjuvanticity of two adjuvant formulations containing de-O-acylated lipooligosaccharide on Japanese encephalitis vaccine in mice vol.41, pp.2, 2017, https://doi.org/10.1007/s12272-017-0985-z
  2. Innate and Adaptive Immune Responses against Bordetella pertussis and Pseudomonas aeruginosa in a Murine Model of Mucosal Vaccination against Respiratory Infection vol.8, pp.4, 2017, https://doi.org/10.3390/vaccines8040647
  3. The Effect of a TLR4 Agonist/Cationic Liposome Adjuvant on Varicella-Zoster Virus Glycoprotein E Vaccine Efficacy: Antigen Presentation, Uptake, and Delivery to Lymph Nodes vol.13, pp.3, 2017, https://doi.org/10.3390/pharmaceutics13030390