1887

Abstract

The aim of this study was to develop an immunogenic protective product against by employing a simple and safe heat treatment-based strategy.

The physicochemical characteristics of naturally produced (OMV) and heat-induced (HT) outer-membrane vesicles from were examined, including a comparison of the protein content of the products. Toxicological and biodistribution studies, and a preliminary experiment to examine the protective effectiveness of HT in a murine model of infection, were also included.

This method simultaneously achieves complete bacterial inactivation and the production of the HT vaccine product, leading to a safe working process. The obtained HT complex presented a similar morphology (electron microscopy) and chemical composition to the classical OMV, although it was enriched in some immunogens, such as lipoproteins, OmpA or OmpC, among others. The HT formulation was not toxic and biodistribution studies performed in mice demonstrated that the vaccine product remained in the small intestine after nasal administration. Finally, a single dose of HT administered nasally was able to protect mice against 2a.

The convenient and safe manufacturing process, and the preliminary biological evaluation, support the use of the self-adjuvanted HT complex as a new vaccine candidate to face shigellosis. Further development is required, such as additional immune analyses, to evaluate whether this new subunit vaccine can be useful in achieving full protection against

Keyword(s): outer-membrane and Shigella
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2017-07-01
2024-04-19
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References

  1. Lamberti LM, Bourgeois AL, Fischer Walker CL, Black RE, Sack D. Estimating diarrheal illness and deaths attributable to Shigellae and enterotoxigenic Escherichia coli among older children, adolescents, and adults in South Asia and Africa. PLoS Negl Trop Dis 2014; 8:e2705 [View Article][PubMed]
    [Google Scholar]
  2. Kirk MD, Pires SM, Black RE, Caipo M, Crump JA et al. World Health Organization estimates of the global and regional disease burden of 22 foodborne bacterial, protozoal, and viral diseases, 2010: a data synthesis. PLoS Med 2015; 12:e1001921 [View Article][PubMed]
    [Google Scholar]
  3. Tilanus A, Mertens R, Seyler L, Lacor P, Velkeniers B. Reactive arthritis due to Shigella infection after a visit to Egypt: a late complication of an intestinal infection. Case Rep Gastrointest Med 2012; 2012:3 [View Article][PubMed]
    [Google Scholar]
  4. Ashkenazi S, Levy I, Kazaronovski V, Samra Z. Growing antimicrobial resistance of Shigella isolates. J Antimicrob Chemother 2003; 51:427–429 [View Article][PubMed]
    [Google Scholar]
  5. Mani S, Wierzba T, Walker RI. Status of vaccine research and development for Shigella. Vaccine 2016; 34:2887–2894 [View Article][PubMed]
    [Google Scholar]
  6. Kaminski RW, Wu M, Turbyfill KR, Clarkson K, Tai B et al. Development and preclinical evaluation of a trivalent, formalin-inactivated Shigella whole-cell vaccine. Clin Vaccine Immunol 2014; 21:366–382 [View Article][PubMed]
    [Google Scholar]
  7. Kämpf MM, Braun M, Sirena D, Ihssen J, Thöny-Meyer L et al. In vivo production of a novel glycoconjugate vaccine against Shigella flexneri 2a in recombinant Escherichia coli: identification of stimulating factors for in vivo glycosylation. Microb Cell Fact 2015; 14:12 [View Article][PubMed]
    [Google Scholar]
  8. Passwell JH, Ashkenzi S, Banet-Levi Y, Ramon-Saraf R, Farzam N et al. Age-related efficacy of Shigella O-specific polysaccharide conjugates in 1-4-year-old Israeli children. Vaccine 2010; 28:2231–2235 [View Article][PubMed]
    [Google Scholar]
  9. Pore D, Chakrabarti MK. Outer membrane protein A (OmpA) from Shigella flexneri 2a: a promising subunit vaccine candidate. Vaccine 2013; 31:3644–3650 [View Article][PubMed]
    [Google Scholar]
  10. Martinez-Becerra FJ, Kissmann JM, Diaz-Mcnair J, Choudhari SP, Quick AM et al. Broadly protective Shigella vaccine based on type III secretion apparatus proteins. Infect Immun 2012; 80:1222–1231 [View Article][PubMed]
    [Google Scholar]
  11. Rossi O, Pesce I, Giannelli C, Aprea S, Caboni M et al. Modulation of endotoxicity of Shigella generalized modules for membrane antigens (GMMA) by genetic lipid A modifications: relative activation of TLR4 and TLR2 pathways in different mutants. J Biol Chem 2014; 289:24922–24935 [View Article][PubMed]
    [Google Scholar]
  12. Roier S, Blume T, Klug L, Wagner GE, Elhenawy W et al. A basis for vaccine development: comparative characterization of Haemophilus influenzae outer membrane vesicles. Int J Med Microbiol 2015; 305:298–309 [View Article][PubMed]
    [Google Scholar]
  13. Camacho AI, Souza-Rebouças J, Irache JM, Gamazo C. Towards a non-living vaccine against Shigella flexneri: from the inactivation procedure to protection studies. Methods 2013; 60:264–268 [View Article][PubMed]
    [Google Scholar]
  14. Ferrari G, Garaguso I, Adu-Bobie J, Doro F, Taddei AR et al. Outer membrane vesicles from group B Neisseria meningitidis Δgna33 mutant: proteomic and immunological comparison with detergent-derived outer membrane vesicles. Proteomics 2006; 6:1856–1866 [View Article][PubMed]
    [Google Scholar]
  15. Maggiore L, Yu L, Omasits U, Rossi O, Dougan G et al. Quantitative proteomic analysis of Shigella flexneri and Shigella sonnei Generalized Modules for Membrane Antigens (GMMA) reveals highly pure preparations. Int J Med Microbiol 2016; 306:99–108 [View Article][PubMed]
    [Google Scholar]
  16. Henry T, Pommier S, Journet L, Bernadac A, Gorvel JP et al. Improved methods for producing outer membrane vesicles in gram-negative bacteria. Res Microbiol 2004; 155:437–446 [View Article][PubMed]
    [Google Scholar]
  17. Mitra S, Sinha R, Mitobe J, Koley H. Development of a cost-effective vaccine candidate with outer membrane vesicles of a tolA-disrupted Shigella boydii strain. Vaccine 2016; 34:1839–1846 [View Article][PubMed]
    [Google Scholar]
  18. Bai X, Findlow J, Borrow R. Recombinant protein meningococcal serogroup B vaccine combined with outer membrane vesicles. Expert Opin Biol Ther 2011; 11:969–985 [View Article][PubMed]
    [Google Scholar]
  19. van de Waterbeemd B, Streefland M, van der Ley P, Zomer B, van Dijken H et al. Improved OMV vaccine against Neisseria meningitidis using genetically engineered strains and a detergent-free purification process. Vaccine 2010; 28:4810–4816 [View Article][PubMed]
    [Google Scholar]
  20. Blasco JM, Gamazo C, Winter AJ, Jiménez de Bagüés MP, Marín C et al. Evaluation of whole cell and subcellular vaccines against Brucella ovis in rams. Vet Immunol Immunopathol 1993; 37:257–270 [View Article][PubMed]
    [Google Scholar]
  21. Ochoa-Repáraz J, Sesma B, Alvarez M, Jesús Renedo M, Irache JM et al. Humoral immune response in hens naturally infected with Salmonella enteritidis against outer membrane proteins and other surface structural antigens. Vet Res 2004; 35:291–298 [View Article][PubMed]
    [Google Scholar]
  22. Schertzer JW, Whiteley M. A bilayer-couple model of bacterial outer membrane vesicle biogenesis. MBio 2012; 3:e00297-11 [View Article][PubMed]
    [Google Scholar]
  23. Katsui N, Tsuchido T, Hiramatsu R, Fujikawa S, Takano M et al. Heat-induced blebbing and vesiculation of the outer membrane of Escherichia coli. J Bacteriol 1982; 151:1523–1531[PubMed]
    [Google Scholar]
  24. Camacho AI, de Souza J, Sánchez-Gómez S, Pardo-Ros M, Irache JM et al. Mucosal immunization with Shigella flexneri outer membrane vesicles induced protection in mice. Vaccine 2011; 29:8222–8229 [View Article][PubMed]
    [Google Scholar]
  25. Dubray G, Limet J. Evidence of heterogeneity of lipopolysaccharides among Brucella biovars in relation to A and M specificities. Ann Inst Pasteur Microbiol 1987; 138:27–37 [View Article][PubMed]
    [Google Scholar]
  26. Bai J, Kim SI, Ryu S, Yoon H. Identification and characterization of outer membrane vesicle-associated proteins in Salmonella enterica serovar Typhimurium. Infect Immun 2014; 82:4001–4010 [View Article][PubMed]
    [Google Scholar]
  27. Brudal E, Lampe EO, Reubsaet L, Roos N, Hegna IK et al. Vaccination with outer membrane vesicles from Francisella noatunensis reduces development of francisellosis in a zebrafish model. Fish Shellfish Immunol 2015; 42:50–57 [View Article][PubMed]
    [Google Scholar]
  28. Gaillard ME, Bottero D, Errea A, Ormazábal M, Zurita ME et al. Acellular pertussis vaccine based on outer membrane vesicles capable of conferring both long-lasting immunity and protection against different strain genotypes. Vaccine 2014; 32:931–937 [View Article][PubMed]
    [Google Scholar]
  29. Kim OY, Hong BS, Park KS, Yoon YJ, Choi SJ et al. Immunization with Escherichia coli outer membrane vesicles protects bacteria-induced lethality via Th1 and Th17 cell responses. J Immunol 2013; 190:4092–4102 [View Article][PubMed]
    [Google Scholar]
  30. Nieves W, Petersen H, Judy BM, Blumentritt CA, Russell-Lodrigue K et al. A Burkholderia pseudomallei outer membrane vesicle vaccine provides protection against lethal sepsis. Clin Vaccine Immunol 2014; 21:747–754 [View Article][PubMed]
    [Google Scholar]
  31. European Medicines Agency 2013; Authorization Details for Bexsero. Available from www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/002333/human_med_001614.jsp&mid = WC0b01ac058001d124
  32. Collins BS. Gram-negative outer membrane vesicles in vaccine development. Discov Med 2011; 12:7–15[PubMed]
    [Google Scholar]
  33. Klimentová J, Stulík J. Methods of isolation and purification of outer membrane vesicles from gram-negative bacteria. Microbiol Res 2015; 170:1–9 [View Article][PubMed]
    [Google Scholar]
  34. Acevedo R, Fernández S, Zayas C, Acosta A, Sarmiento ME et al. Bacterial outer membrane vesicles and vaccine applications. Front Immunol 2014; 5:121 [View Article][PubMed]
    [Google Scholar]
  35. van de Waterbeemd B, Zomer G, Kaaijk P, Ruiterkamp N, Wijffels RH et al. Improved production process for native outer membrane vesicle vaccine against Neisseria meningitidis. PLoS One 2013; 8:e65157 [View Article][PubMed]
    [Google Scholar]
  36. Berlanda Scorza F, Colucci AM, Maggiore L, Sanzone S, Rossi O et al. High yield production process for Shigella outer membrane particles. PLoS One 2012; 7:e35616 [View Article][PubMed]
    [Google Scholar]
  37. van der Pol L, Stork M, van der Ley P. Outer membrane vesicles as platform vaccine technology. Biotechnol J 2015; 10:1689–1706 [View Article][PubMed]
    [Google Scholar]
  38. McKenzie R, Walker RI, Nabors GS, van de Verg LL, Carpenter C et al. Safety and immunogenicity of an oral, inactivated, whole-cell vaccine for Shigella sonnei: preclinical studies and a phase I trial. Vaccine 2006; 24:3735–3745 [View Article][PubMed]
    [Google Scholar]
  39. Mukhopadhaya A, Mahalanabis D, Khanam J, Chakrabarti MK. Protective efficacy of oral immunization with heat-killed Shigella flexneri 2a in animal model: study of cross protection, immune response and antigenic recognition. Vaccine 2003; 21:3043–3050 [View Article][PubMed]
    [Google Scholar]
  40. Gamazo C, Winter AJ, Moriyón I, Riezu-Boj JI, Blasco JM et al. Comparative analyses of proteins extracted by hot saline or released spontaneously into outer membrane blebs from field strains of Brucella ovis and Brucella melitensis. Infect Immun 1989; 57:1419–1426[PubMed]
    [Google Scholar]
  41. Bonnington KE, Kuehn MJ. Protein selection and export via outer membrane vesicles. Biochim Biophys Acta 2014; 1843:1612–1619 [View Article][PubMed]
    [Google Scholar]
  42. Rajsekhar B, Chakrabarti M. Outer membrane protein A (OmpA) of Shigella flexneri 2a induces B cell activation and protective immune response in mouse model. Faseb J 2015; 29:
    [Google Scholar]
  43. Mukhopadhaya A, Mahalanabis D, Chakrabarti MK. Role of Shigella flexneri 2a 34 kDa outer membrane protein in induction of protective immune response. Vaccine 2006; 24:6028–6036 [View Article][PubMed]
    [Google Scholar]
  44. Pore D, Mahata N, Pal A, Chakrabarti MK. Outer membrane protein A (OmpA) of Shigella flexneri 2a, induces protective immune response in a mouse model. PLoS One 2011; 6:e22663 [View Article][PubMed]
    [Google Scholar]
  45. Pieper R, Fisher CR, Suh MJ, Huang ST, Parmar P et al. Analysis of the proteome of intracellular Shigella flexneri reveals pathways important for intracellular growth. Infect Immun 2013; 81:4635–4648 [View Article][PubMed]
    [Google Scholar]
  46. Wang X, Jiang F, Zheng J, Chen L, Dong J et al. The outer membrane phospholipase A is essential for membrane integrity and type III secretion in Shigella flexneri. Open Biol 2016; 6:160073 [View Article][PubMed]
    [Google Scholar]
  47. McClean S. Eight stranded β-barrel and related outer membrane proteins: role in bacterial pathogenesis. Protein Pept Lett 2012; 19:1013–1025 [View Article][PubMed]
    [Google Scholar]
  48. Casey WT, Spink N, Cia F, Collins C, Romano M et al. Identification of an OmpW homologue in Burkholderia pseudomallei, a protective vaccine antigen against melioidosis. Vaccine 2016; 34:2616–2621 [View Article][PubMed]
    [Google Scholar]
  49. Kim KH, Aulakh S, Paetzel M. The bacterial outer membrane β-barrel assembly machinery. Protein Sci 2012; 21:751–768 [View Article][PubMed]
    [Google Scholar]
  50. Aliprantis AO, Weiss DS, Radolf JD, Zychlinsky A. Release of toll-like receptor-2-activating bacterial lipoproteins in Shigella flexneri culture supernatants. Infect Immun 2001; 69:6248–6255 [View Article][PubMed]
    [Google Scholar]
  51. Brightbill HD, Libraty DH, Krutzik SR, Yang RB, Belisle JT et al. Host defense mechanisms triggered by microbial lipoproteins through toll-like receptors. Science 1999; 285:732–736 [View Article][PubMed]
    [Google Scholar]
  52. Fletcher LD, Bernfield L, Barniak V, Farley JE, Howell A et al. Vaccine potential of the Neisseria meningitidis 2086 lipoprotein. Infect Immun 2004; 72:2088–2100 [View Article][PubMed]
    [Google Scholar]
  53. Masignani V, Comanducci M, Giuliani MM, Bambini S, Adu-Bobie J et al. Vaccination against Neisseria meningitidis using three variants of the lipoprotein GNA1870. J Exp Med 2003; 197:789–799 [View Article][PubMed]
    [Google Scholar]
  54. Wressnigg N, Barrett PN, Pöllabauer EM, O'Rourke M, Portsmouth D et al. A novel multivalent OspA vaccine against Lyme borreliosis is safe and immunogenic in an adult population previously infected with Borrelia burgdorferi sensu lato. Clin Vaccine Immunol 2014; 21:1490–1499 [View Article][PubMed]
    [Google Scholar]
  55. Thakran S, Li H, Lavine CL, Miller MA, Bina JE et al. Identification of Francisella tularensis lipoproteins that stimulate the toll-like receptor (TLR) 2/TLR1 heterodimer. J Biol Chem 2008; 283:3751–3760 [View Article][PubMed]
    [Google Scholar]
  56. Zariri A, Beskers J, van de Waterbeemd B, Hamstra HJ, Bindels TH et al. Meningococcal outer membrane vesicle composition-dependent activation of the innate immune response. Infect Immun 2016; 84:3024–3033 [View Article][PubMed]
    [Google Scholar]
  57. Bernardini ML, Sanna MG, Fontaine A, Sansonetti PJ. OmpC is involved in invasion of epithelial cells by Shigella flexneri. Infect Immun 1993; 61:3625–3635[PubMed]
    [Google Scholar]
  58. Kaminski RW, Clarkson K, Kordis AA, Oaks EV. Multiplexed immunoassay to assess Shigella-specific antibody responses. J Immunol Methods 2013; 393:18–29 [View Article][PubMed]
    [Google Scholar]
  59. Oaks EV, Turbyfill KR. Development and evaluation of a Shigella flexneri 2a and S. sonnei bivalent invasin complex (Invaplex) vaccine. Vaccine 2006; 24:2290–2301 [View Article][PubMed]
    [Google Scholar]
  60. Sellge G, Magalhaes JG, Konradt C, Fritz JH, Salgado-Pabon W et al. Th17 cells are the dominant T cell subtype primed by Shigella flexneri mediating protective immunity. J Immunol 2010; 184:2076–2085 [View Article][PubMed]
    [Google Scholar]
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