1887

Abstract

is a significant bacterial pathogen in humans. Currently, there are two types of pneumococcal vaccines, but there are concerns regarding their application.

Since many pneumococcal proteins are serotype-independent, polyhistidine triad protein D (PhtD) has been selected as a vaccine candidate.

We prepared recombinant PhtD and its C-terminal fragment (PhtD-C) using alum and outer-membrane vesicles (OMVs) as adjuvants. The combinations were injected intraperitoneally into mice, and then total immunoglobulin G (IgG) and specific IgG, IgG1 and IgG2a were measured. A serum bactericidal assay and opsonophagocytosis were also performed as complementary tests. Meningococcal OMVs were used as an adjuvant.

The levels of specific IgG and IgG1 against combinations of PhtD and its C-terminal with OMVs and alum as adjuvants increased at the time of the third mouse immunization on day 35. Forty per cent and 60% of ATCC 6303 (serotype 3) as a virulent pneumococcal strain, respectively, were killed in the opsonophagocytosis test and these results could also be observed in the serum bactericidal assay. Mice mmunized iwith PhtD and its C-terminal with OMVs and alum as adjuvants survived after 10 days of pneumococcal challenge.

The combination of PhtD and PhtD-C with alum produced optimal results, but the combination of PhtD and PhtD-C with OMVs produced minimal results by comparison. The survival rates were also measured, and these corresponded with the results of the immunological assessments. Our findings showed that mice receiving PhtD and PhtD-C plus OMV and alum had higher survival rates than the mice in the other groups.

Funding
This study was supported by the:
  • Pasteur Institute of Iran
    • Principle Award Recipient: seyed fazlollah mousavi
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2020-02-25
2024-11-05
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References

  1. Weiser JN, Ferreira DM, Paton JC. Streptococcus pneumoniae: transmission, colonization and invasion. Nat Rev Microbiol 2018; 16:355–367 [View Article]
    [Google Scholar]
  2. Cherazard R, Epstein M, Doan TL, Salim T, Bharti S et al. Antimicrobial resistant Streptococcus pneumoniae: prevalence, mechanisms, and clinical implications. Am J Ther 2017; 24:e361–369 [View Article]
    [Google Scholar]
  3. Kim L, McGee L, Tomczyk S, Beall B. Biological and epidemiological features of antibiotic-resistant Streptococcus pneumoniae in pre- and Post-conjugate vaccine eras: a United States perspective. Clin Microbiol Rev 2016; 29:525–552 [View Article]
    [Google Scholar]
  4. Feldman C, Anderson R. Review: current and new generation pneumococcal vaccines. J Infect 2014; 69:309–325 [View Article]
    [Google Scholar]
  5. Ogunniyi AD, Grabowicz M, Briles DE, Cook J, Paton JC. Development of a vaccine against invasive pneumococcal disease based on combinations of virulence proteins of Streptococcus pneumoniae . Infect Immun 2007; 75:350–357 [View Article]
    [Google Scholar]
  6. Ogunniyi AD, Mahdi LK, Trappetti C, Verhoeven N, Mermans D et al. Identification of genes that contribute to the pathogenesis of invasive pneumococcal disease by in vivo transcriptomic analysis. Infect Immun 2012; 80:3268–3278 [View Article]
    [Google Scholar]
  7. Adamou JE, Heinrichs JH, Erwin AL, Walsh W, Gayle T et al. Identification and characterization of a novel family of pneumococcal proteins that are protective against sepsis. Infect Immun 2001; 69:949–958 [View Article]
    [Google Scholar]
  8. Rioux S, Neyt C, Di Paolo E, Turpin L, Charland N et al. Transcriptional regulation, occurrence and putative role of the Pht family of Streptococcus pneumoniae . Microbiology 2011; 157:336–348 [View Article]
    [Google Scholar]
  9. Zhang Y, Masi AW, Barniak V, Mountzouros K, Hostetter MK et al. Recombinant PhpA protein, a unique histidine motif-containing protein from Streptococcus pneumoniae, protects mice against intranasal pneumococcal challenge. Infect Immun 2001; 69:3827–3836 [View Article]
    [Google Scholar]
  10. Plumptre CD, Ogunniyi AD, Paton JC. Surface association of Pht proteins of Streptococcus pneumoniae . Infect Immun 2013; 81:3644–3651 [View Article]
    [Google Scholar]
  11. Beghetto E, Gargano N, Ricci S, Garufi G, Peppoloni S et al. Discovery of novel Streptococcus pneumoniae antigens by screening a whole-genome lambda-display library. FEMS Microbiol Lett 2006; 262:14–21 [View Article]
    [Google Scholar]
  12. Malley R, Anderson PW. Serotype-independent pneumococcal experimental vaccines that induce cellular as well as humoral immunity. Proc Natl Acad Sci U S A 2012; 109:3623–3627 [View Article]
    [Google Scholar]
  13. Hamel J, Charland N, Pineau I, Ouellet C, Rioux S et al. Prevention of pneumococcal disease in mice immunized with conserved surface-accessible proteins. Infect Immun 2004; 72:2659–2670 [View Article]
    [Google Scholar]
  14. Verhoeven D, Xu Q, Pichichero ME. Vaccination with a Streptococcus pneumoniae trivalent recombinant PcpA, PhtD and PlyD1 protein vaccine candidate protects against lethal pneumonia in an infant murine model. Vaccine 2014; 32:3205–3210 [View Article]
    [Google Scholar]
  15. Plumptre CD, Ogunniyi AD, Paton JC. Vaccination against Streptococcus pneumoniae using truncated derivatives of polyhistidine triad protein D. PLoS One 2013; 8:e78916 [View Article]
    [Google Scholar]
  16. Godfroid F, Hermand P, Verlant V, Denoël P, Poolman JT. Preclinical evaluation of the Pht proteins as potential cross-protective pneumococcal vaccine antigens. Infect Immun 2011; 79:238–245 [View Article]
    [Google Scholar]
  17. Plumptre CD, Ogunniyi AD, Paton JC. Polyhistidine triad proteins of pathogenic streptococci. Trends Microbiol 2012; 20:485–493 [View Article]
    [Google Scholar]
  18. Seiberling M, Bologa M, Brookes R, Ochs M, Go K et al. Safety and immunogenicity of a pneumococcal histidine triad protein D vaccine candidate in adults. Vaccine 2012; 30:7455–7460 [View Article]
    [Google Scholar]
  19. Awate S, Babiuk LA, Mutwiri G. Mechanisms of action of adjuvants. Front Immunol 2013; 4:114 [View Article]
    [Google Scholar]
  20. Jan AT. Outer membrane vesicles (OMVs) of gram-negative bacteria: a perspective update. Front Microbiol 2017; 8:1053 [View Article]
    [Google Scholar]
  21. Tan K, Li R, Huang X, Liu Q. Outer membrane vesicles: current status and future direction of these novel vaccine adjuvants. Front Microbiol 2018; 9:783 [View Article]
    [Google Scholar]
  22. Mierendorf RC, Morris BB, Hammer B, Novy RE. Expression and purification of recombinant proteins using the pET system. Methods Mol Med 1998; 13:257–292 [View Article]
    [Google Scholar]
  23. Sambrook J, Russell DWS. The Condensed Protocols from Molecular Cloning: a Laboratory Manual New York: Cold Spring Harbor Laboratory Press; 2006
    [Google Scholar]
  24. Afrough P, Bouzari S, Mousavi SF, Asadi Karam MR, Vaziri F et al. Evaluation of immunological responses to recombinant Porin A protein (rPoA) from native strains of Neisseria meningitidis serogroups A and B using OMV as an adjuvant in BALB/c mice. Microb Pathog 2017; 112:209–214 [View Article]
    [Google Scholar]
  25. Siadat SD, Behzadiannejad G, Tabaraie B, Najar-Peerayeh S, Ahmadi H. Extraction and Molecular Evaluation of Neisseria meningitidis Serogroup B Outer Membrane Vesicle Containing PorA 65 Daneshvar Medicine, scientific-research journal of shahed university; 2006 pp 32–37
    [Google Scholar]
  26. Siadat SD, Tabaraie B, Behzadiannejad Q, Norouziuan D, Ahmadi H et al. Bactericidal activity of outer membrane vesicle of Neisseria meningitidis serogroup b as a vaccine candidate in animal model. Iran J Infect Dis Trop Med 2007; 12:11–17
    [Google Scholar]
  27. Claassen I, Meylis J, van der Ley P, Peeters C, Brons H et al. Production, characterization and control of a Neisseria meningitidis hexavalent class 1 outer membrane protein containing vesicle vaccine. Vaccine 1996; 14:1001–1008 [View Article]
    [Google Scholar]
  28. Delbaz SA, Siadat SD, Aghasadeghi MR, Piryaie M, Najar Peerayeh S et al. Biological and immunological evaluation of Neisseria meningitidis serogroup a outer membrane vesicle as vaccine candidates. Jundishapur J Microbiol 2013; 6:1–6 [View Article]
    [Google Scholar]
  29. Vipond C, Findlay L, Feavers I, Care R. Limitations of the rabbit pyrogen test for assessing meningococcal OMV based vaccines. ALTEX 2016; 33:47–53 [View Article]
    [Google Scholar]
  30. Goyette-Desjardins G, Roy R, Segura M. Murine whole-blood opsonophagocytosis assay to evaluate protection by antibodies raised against encapsulated extracellular bacteria. Carbohydrate-Based Vaccines New York: Humana Press; 2015 pp 81–92
    [Google Scholar]
  31. Melin M, Di Paolo E, Tikkanen L, Jarva H, Neyt C et al. Interaction of pneumococcal histidine triad proteins with human complement. Infect Immun 2010; 78:2089–2098 [View Article]
    [Google Scholar]
  32. Linley E, Bell A, Gritzfeld JF, Borrow R. Should pneumococcal serotype 3 be included in serotype-specific immunoassays?. Vaccines 2019; 7:4–10 [View Article]
    [Google Scholar]
  33. Sugimoto N, Yamagishi Y, Hirai J, Sakanashi D, Suematsu H et al. Invasive pneumococcal disease caused by mucoid serotype 3 Streptococcus pneumoniae: a case report and literature review. BMC Res Notes 2017; 10:1–6 [View Article]
    [Google Scholar]
  34. Mousavi SF, Nobari S, Rahmati Ghezelgeh F, Lyriai H, Jalali P et al. Serotyping of Streptococcus pneumoniae isolated from Tehran by Multiplex PCR: Are serotypes of clinical and carrier isolates identical?. Iran J Microbiol 2013; 5:220–226
    [Google Scholar]
  35. Khan MN, Pichichero ME. Cd4 T cell memory and antibody responses directed against the pneumococcal histidine triad proteins PhtD and PhtE following nasopharyngeal colonization and immunization and their role in protection against pneumococcal colonization in mice. Infect Immun 2013; 81:3781–3792 [View Article]
    [Google Scholar]
  36. Briles DE, Hollingshead SK. Surface proteins of Streptococcus pneumoniae: their roles in virulence and potential as vaccines. Program and abstracts of the 2006 euroconference on infections and lung diseases. Paris, France 2006
    [Google Scholar]
  37. Giefing C, Meinke AL, Hanner M, Henics T, Minh DB et al. Discovery of a novel class of highly conserved vaccine antigens using genomic scale antigenic fingerprinting of pneumococcus with human antibodies. J Exp Med 2008; 205:117–131 [View Article]
    [Google Scholar]
  38. Bologa M, Kamtchoua T, Hopfer R, Sheng X, Hicks B et al. Safety and immunogenicity of pneumococcal protein vaccine candidates: monovalent choline-binding protein A (PCPA) vaccine and bivalent PcpA-pneumococcal histidine triad protein D vaccine. Vaccine 2012; 30:7461–7468 [View Article]
    [Google Scholar]
  39. Hicks LA, Harrison LH, Flannery B, Hadler JL, Schaffner W et al. Incidence of pneumococcal disease due to non–pneumococcal conjugate vaccine (PCV7) serotypes in the United States during the era of widespread PCV7 vaccination, 1998-2004. J Infect Dis 2007; 196:1346–1354 [View Article]
    [Google Scholar]
  40. Denoël P, Philipp MT, Doyle L, Martin D, Carletti G et al. A protein-based pneumococcal vaccine protects rhesus macaques from pneumonia after experimental infection with Streptococcus pneumoniae . Vaccine 2011; 29:5495–5501 [View Article]
    [Google Scholar]
  41. Pennington SH, Pojar S, Mitsi E, Gritzfeld JF, Nikolaou E et al. Polysaccharide-specific memory B cells predict protection against experimental human pneumococcal carriage. Am J Respir Crit Care Med 2016; 194:1523–1531 [View Article]
    [Google Scholar]
  42. Khan MN, Pichichero ME. Vaccine candidates PhtD and PhtE of Streptococcus pneumoniae are adhesins that elicit functional antibodies in humans. Vaccine 2012; 30:2900–2907 [View Article]
    [Google Scholar]
  43. 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]
    [Google Scholar]
  44. Tan K, Li R, Huang X, Liu Q. Outer membrane vesicles: current status and future direction of these novel vaccine adjuvants. Front Microbiol 2018; 9:1–12 [View Article]
    [Google Scholar]
  45. Sharifat Salmani A, Siadat SD, Norouzian D, Izadi Mobarakeh J, Kheirandish M et al. Outer membrane vesicle of Neisseria meningitidis serogroup B as an adjuvant to induce specific antibody response against the lipopolysaccharide of Brucella abortus S99. Ann Microbiol 2009; 59:145–149 [View Article]
    [Google Scholar]
  46. Farjah A, Owlia P, Siadat SD, Mousavi SF, Ardestani MS et al. Immunological evaluation of an alginate-based conjugate as a vaccine candidate against Pseudomonas aeruginosa . APMIS 2015; 123:175–183 [View Article]
    [Google Scholar]
  47. Kallio A, Sepponen K, Hermand P, Denoël P, Godfroid F et al. Role of Pht proteins in attachment of Streptococcus pneumoniae to respiratory epithelial cells. Infect Immun 2014; 82:1683–1691 [View Article]
    [Google Scholar]
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