DOI QR코드

DOI QR Code

Bactericidal Antibody Responses to Meningococcal Recombinant Outer Membrane Proteins

  • Ming Zhu (Department of Pediatrics, Shandong Provincial Third Hospital, Shandong University) ;
  • Yunqing Sun (Department of Pediatrics, Shandong Provincial Third Hospital, Shandong University)
  • Received : 2024.01.18
  • Accepted : 2024.03.29
  • Published : 2024.07.28

Abstract

Secretin PilQ is an antigenically conserved outer membrane protein that is present in most meningococci and PorA is a major protein that elicits bactericidal immune response in humans following natural disease and immunization. In the present study, BALB/c mice were immunized subcutaneously with rPilQ406-770 or rPorA together with Freund's adjuvant (FA). Serum antibody responses to serogroup A and B Neisseria meningitides whole cells or purified proteins and functional activity of antibodies were determined by ELISA and serum bactericidal assay (SBA), respectively. Serum IgG responses were significantly increased in the immunized group with rPilQ406-770 or rPorA together with FA compared to control groups. IgG antibody response of mice immunized with rPilQ406-770 was significantly more than mice immunized with rPorA (OD at 450 nm was 1.6 versus 0.83). The booster injections were effective in increasing the responses of antirPilQ406-770 or anti-rPorA IgG significantly. Antisera produced against rPilQ406-770 or rPorA demonstrated strong surface reactivity to serogroup B N. meningitides in comparison with control groups. Antisera raised against rPorA or rPilQ406-770 and FA demonstrated SBA titers from 1/1024 to 1/2048 against serogroup B. The strongest bactericidal activity was detected in sera from mice immunized with rPilQ406-770 mixed with FA. These results suggest that rPilQ406-770 is a potential vaccine candidate for serogroup B N. meningitidis.

Keywords

References

  1. Vermont CL, van Dijken HH, Kuipers AJ, van Limpt CJ, Keijzers WC, van der Ende A, et al. 2003. Cross-reactivity of antibodies against PorA after vaccination with a meningococcal B outer membrane vesicle vaccine. Infect. Immun. 71: 1650-1655.
  2. Girard MP, Preziosi MP, Aguado MT, Kieny MP. 2006. A review of vaccine research and development: meningococcal disease. Vaccine 24: 4692-4700.
  3. Sun Y, Li Y, Exley RM, Winterbotham M, Ison C, Smith H, et al. 2005. Identification of novel antigens that protect against systemic meningococcal infection. Vaccine 23: 4136-4141.
  4. Callaghan MJ, Lewis S, Sadarangani M, Bailey SE, Chan H, Ferguson DJ, et al. 2011. Potential of recombinant opa proteins as vaccine candidates against hyperinvasive meningococci. Infect. Immun. 79: 2810-2818.
  5. Araghi M, Mannani R, Heidarnejad maleki A, Hamidi A, Rostami S, Safa SH, et al. 2023. Recent advances in non-small cell lung cancer targeted therapy; an update review. Cancer Cell Int. 23: 162.
  6. Zare Rafie M, Esmaeilzadeh A, Ghoreishi A, Tahmasebi S, Faghihzadeh E, Elahi R. 2021. IL-38 as an early predictor of the ischemic stroke prognosis. Cytokine 146: 155626.
  7. Collins RF, Frye SA, Balasingham S, Ford RC, Tonjum T, Derrick JP. 2005. Interaction with type IV pili induces structural changes in the bacterial outer membrane secretin PilQ. J. Biol. Chem. 280: 18923-18930.
  8. Harrison OB, Robertson BD, Faust SN, Jepson MA, Goldin RD, Levin M, et al. 2002. Analysis of pathogen-host cell interactions in purpura fulminans: expression of capsule, type IV pili, and PorA by Neisseria meningitidis in vivo. Infect. Imun. 70: 5193-5201.
  9. Assalkhou R, Balasingham S, Collins RF, Frye SA, Davidsen T, Benam AV, et al. 2007. The outer membrane secretin PilQ from Neisseria meningitidis binds DNA. Microbiology (Reading, England) 153: 1593-1603.
  10. Feavers IM, Pizza M. 2009. Meningococcal protein antigens and vaccines. Vaccine 27 Suppl 2: B42-50.
  11. Frye SA, Assalkhou R, Collins RF, Ford RC, Petersson C, Derrick JP, et al. 2006. Topology of the outer-membrane secretin PilQ from Neisseria meningitidis. Microbiology (Reading, England) 152: 3751-3764.
  12. Poolman JT, Denoel P, Feron C, Goraj K, Weynants V. 2006. Outer mmbrane vsicle-based mningococcal vccines. Handbook of Meningococcal Disease: Infection Biology, Vaccination, Clinical Management pp. 371-390.
  13. Peeters CC, Rumke HC, Sundermann LC, Rouppe van der Voort EM, Meulenbelt J, Schuller M, et al. 1996. Phase I clinical trial with a hexavalent PorA containing meningococcal outer membrane vesicle vaccine. Vaccine 14: 1009-1015.
  14. van der Ende A, Hopman CT, Zaat S, Essink BB, Berkhout B, Dankert J. 1995. Variable expression of class 1 outer membrane protein in Neisseria meningitidis is caused by variation in the spacing between the -10 and -35 regions of the promoter. J. Bcteriol. 177: 2475-2480.
  15. Arigita C, Bevaart L, Everse LA, Koning GA, Hennink WE, Crommelin DJ, et al. 2003. Liposomal meningococcal B vaccination: role of dendritic cell targeting in the development of a protective immune response. Infect. Imun. 71: 5210-5218.
  16. Haghi F, NAJAR PS, Siadat SD, Mahdavi M. 2010. Cloning, expression and purification of outer membrane secretin PilQ406-770 of Neisseria meningitidis serogroup B. Iranian J. Clin. Infect. Dis. 4: 193-199.
  17. Haghi F, Peerayeh SN, Siadat SD, Montajabiniat M. 2011. Cloning, expression and purification of outer membrane protein PorA of Neisseria meningitidis serogroup B. J. Infect. Dev. Ctries. 5: 856-862.
  18. Welsch JA, Granoff D. 2007. Immunity to Neisseria meningitidis group B in adults despite lack of serum bactericidal antibody. Clin. Vaccine Immunol. 14: 1596-1602.
  19. Ciabattini A, Giomarelli B, Parigi R, Chiavolini D, Pettini E, Arico B, et al. 2008. Intranasal immunization of mice with recombinant Streptococcus gordonii expressing NadA of Neisseria meningitidis induces systemic bactericidal antibodies and local IgA. Vaccine 26: 4244-4250.
  20. Humphries HE, Williams JN, Blackstone R, Jolley KA, Yuen HM, Christodoulides M, et al. 2006. Multivalent liposome-based vaccines containing different serosubtypes of PorA protein induce cross-protective bactericidal immune responses against Neisseria meningitidis. Vaccine 24: 36-44.
  21. Rezaei N, Aghamohammadi A, Siadat SD, Moin M, Pourpak Z, Nejati M, et al. 2008. Serum bactericidal antibody responses to meningococcal polysaccharide vaccination as a basis for clinical classification of common variable immunodeficiency. Clin. Vaccine Immunol. 15: 607-611.
  22. Rezaei N, Aghamohammadi A, Siadat SD, Nejati M, Ahmadi H, Moin M, et al. 2007. Serum bactericidal antibody response to serogroup C polysaccharide meningococcal vaccination in children with primary antibody deficiencies. Vaccine 25: 5308-5314.
  23. Abdolmohammadi K, Mahmoudi T, Alimohammadi M, Tahmasebi S, Zavvar M, Hashemi SM. 2023. Mesenchymal stem cell-based therapy as a new therapeutic approach for acute inflammation. Life Sci. 312: 121206.
  24. Eshghi F, Tahmasebi S, Alimohammadi M, Soudi S, Khaligh SG, Khosrojerdi A, et al. 2022. Study of immunomodulatory effects of mesenchymal stem cell-derived exosomes in a mouse model of LPS induced systemic inflammation. Life Sci. 310: 120938.
  25. Jafari D, Mousavi MJ, Keshavarz Shahbaz S, Jafarzadeh L, Tahmasebi S, Spoor J, et al. 2021. E3 ubiquitin ligase Casitas B lineage lymphoma-b and its potential therapeutic implications for immunotherapy. Clin. Exper. Immunol. 204: 14-31.
  26. Tonjum T, Koomey M. 1997. The pilus colonization factor of pathogenic neisserial species: organelle biogenesis and structure/function relationships--a review. Gene 192: 155-163.
  27. Collins RF, Ford RC, Kitmitto A, Olsen RO, Tonjum T, Derrick JP. 2003. Three-dimensional structure of the Neisseria meningitidis secretin PilQ determined from negative-stain transmission electron microscopy. J. Bacteriol. 185: 2611-2617.
  28. Halliwell D, Frye S, Taylor S, Flockhart A, Finney M, Reddin K, et al. 2004. Presented at the 14th International Pathogenic Neisseria Conference. USA.
  29. Massari P, Ram S, Macleod H, Wetzler LM. 2003. The role of porins in neisserial pathogenesis and immunity. Trends Microbiol. 11: 87-93.
  30. Humphries HE, Christodoulides M, Heckels JE. 2002. Expression of the class 1 outer-membrane protein of Neisseria meningitidis in Escherichia coli and purification using a self-cleavable affinity tag. Protein Expr. Purif. 26: 243-248.
  31. van der Ende A, Hopman CT, Dankert J. 2000. Multiple mechanisms of phase variation of PorA in Neisseria meningitidis. Infect. Immun. 68: 6685-6690.
  32. van den Elsen J, Vandeputte-Rutten L, Kroon J, Gros P. 1999. Bactericidal antibody recognition of meningococcal PorA by induced fit. comparison of liganded and unliganded Fab structures. J. Biol. Chem. 274: 1495-1501.
  33. Trotter CL, Ramsay ME. 2007. Vaccination against meningococcal disease in Europe: review and recommendations for the use of conjugate vaccines. FEMS Microbiol. Rev. 31: 101-107.