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A Vaccine for Nontypable Haemophilus influenzae

  • Allan W. Cripps
  • Jennelle M. Kyd
Part of the Medical Intelligence Unit book series (MIUN)

Summary

Nontypable H. influenzae (NTHI) is a common commensal of the upper respiratory tract residing in both the nasopharynx and the posterior oropharynx. It is one of the leading causative bacterial pathogens of otitis media (OM) in children and serious urogenital, neonatal and mother-infant infections. It is also the cause of significant morbidity in patients with pulmonary diseases such as cystic fibrosis and chronic obstructive pulmonary disease. NTHI colonizes the respiratory tract through adherence to the mucous and epithelial cells. It has several bacterial surface components that have the capacity to facilitate adherence and interactions between the bacterium and epithelial cells, setting the stage for the cycle of inflammation. Whole killed cell or bacterial extracts have been investigated in human trials providing results that demonstrate the potential for a vaccine to protect against infection. Several lead candidate antigens have been proposed based on studies in animal models but have yet to be formulated for human trials. The composition of a vaccine requires that the antigens be conserved among strains, immunogenic and protective against infection and that the delivery of the vaccine results in the relevant immune response, probably a balance of specific cellular and humoral responses.

Keywords

Chronic Obstructive Pulmonary Disease Chronic Bronchitis Haemophilus Influenzae Outer Membrane Protein Acute Bronchitis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Pfeiffer R. Vorlaufige mittheilungen ber die errenger der influenza. Deutsche medizinische Wochenschrift 1892; 18:28.CrossRefGoogle Scholar
  2. 2.
    Winslow CEA, Broadhurst J, Buchanan RE. The families and genera of the bacteria. Final report of the Society of American Bacteriologists on characterization and classification of beacterial types. J Bacteriol 1920; 5:191–229.PubMedGoogle Scholar
  3. 3.
    Smith W, Hale JH, O’Callaghan. Haem utilisation and nitrate reduction by Haemophilus influenzae. J Path Bact 1933; 65:229–238.CrossRefGoogle Scholar
  4. 4.
    Turk DC, May JR. Haemophilus influenzae as a pathogen. In: Haemophilus influenzae: Its clinical importance. First ed. English Universities Press, 1967:24–26.Google Scholar
  5. 5.
    May JR. Chemotherapy of chronic bronchitis and allied disorders. 2nd ed. London: English Universities Press, 1972.Google Scholar
  6. 6.
    Butt HL, Clancy RL, Cripps AW et al. Bacterial colonization of the respiratory tract in chronic bronchitis. Aust NZ J Med 1990; 20:35–38.CrossRefGoogle Scholar
  7. 7.
    van Belkum A, Struelens M, de Visser A et al. Role of genomic typing in taxonomy, evolutionary genetics, and microbial epidemiology. Clin Microbiol Rev 2001; 14:547–60.PubMedCrossRefGoogle Scholar
  8. 8.
    Dhooge I, Vaneechoutte M, Claeys G et al. Turnover of Haemophilus influenzae isolates in otitis-prone children. Int J Pediatr Otorhinolaryngol 2000; 54:7–12.PubMedCrossRefGoogle Scholar
  9. 9.
    van Alphen L, Caugant DA, Duim B et al. Differences in genetic diversity of nonecapsulated Haemophilus influenzae from various diseases. Microbiol 1997; 143:1423–1431.CrossRefGoogle Scholar
  10. 10.
    Smith-Vaughan HC, Sriprakash KS, Leach AJ et al. Low genetic diversity of Haemophilus influenzae type b compared to nonencapsulated H. influenzae in a population in which H. influenzae is highly endemic. Infect Immun 1998; 66:3403–9.PubMedGoogle Scholar
  11. 11.
    Harper JJ, Tilse MH. Biotypes of Haemophilus influenzae that are associated with noninvasive infection. J Clin Microbiol 1991; 29:2539–2542.PubMedGoogle Scholar
  12. 12.
    Quentin R, Goudeau A, Wallace RJ Jr et al. Urogenital, maternal and neonatal isolates of Haemophilus influenzae: Identification of unusually virulent serologically non-typable clone families and evidence for new Haemophilus species. J Gen Microbiol 1990; 136:1203–1209.PubMedCrossRefGoogle Scholar
  13. 13.
    Weinberg GA, Lehmann D, Tupasi TE et al. Diversity of outer membrane protein profiles of nontypable Haemophilus influenzae from children from Papua New Guinea and the Philipines. Rev Infect Dis 1990; 12:1017–1020.CrossRefGoogle Scholar
  14. 14.
    van Schilfgaarde M, van Ulsen P, Eijk P et al. Characterization of adherence of nontypeable Haemophilus influenzae to human epithelial cells. Infect Immun 2000; 68:4658–4665.PubMedCrossRefGoogle Scholar
  15. 15.
    Claesson BA, Lagergard T, Trollfors B. Antibody response to outer membrane of noncapsulated Haemophilus influenzae isolated from the nasopharynx of children with pneumonia. Pediatr Infect Dis J 1991; 10:104–108.PubMedCrossRefGoogle Scholar
  16. 16.
    Gratten M, Gratten H, Poli A et al. Colonisation of Haemophilus influenzae and Streptococcus pneumoniae in the upper respiratory tract of neonates in Papua New Guinea: primary acquisition, duration of carriage, and relationship to carriage in mothers. Biol Neonate 1986; 50:114–20.PubMedCrossRefGoogle Scholar
  17. 17.
    Giebink GS. Immunoprophylaxis of otitis media. Adv Exp Med Biol 1991; 303:149–58.PubMedCrossRefGoogle Scholar
  18. 18.
    Harabuchi Y, Faden H, Yamanaka N et al. Nasopharyngeal colonization with nontypeable Haemophilus influenzae and recurrent otitis media. J Infect Dis 1994; 170:862–866.PubMedCrossRefGoogle Scholar
  19. 19.
    St Geme III JW. The pathogenesis of nontypeable Haemophilus influenzae otitis media. Vaccine 2001; 19:S41–S50.CrossRefGoogle Scholar
  20. 20.
    Faden H, Duffy L, Wasielewski R et al. Relationships between nasopharyngeal colonization and the development of otitis media in children. J Infect Dis 1997; 175:1440–1445.PubMedCrossRefGoogle Scholar
  21. 21.
    Leach AJ, Boswell JB, Asche V et al. Bacterial colonisation of the nasopharynx predicts very early onset and persistence of otitis media in Australian Aboriginal infants. Pediatr Infect Dis J 1994; 13:983–989.PubMedCrossRefGoogle Scholar
  22. 22.
    Cote S, Sanschagrin F, Dargis M et al. Molecular typing of Haemophilus influenzae using a DNA probe and multiplex PCR. Mol Cell Probes 1994; 8:23–37.PubMedCrossRefGoogle Scholar
  23. 23.
    Wallace RJ, Jr., Baker CJ, Quinones FJ et al. Nontypable Haemophilus influenzae (biotype 4) as a neonotal, maternal, and genital pathogen. Rev Infect Dis 1983; 5:123–136.PubMedCrossRefGoogle Scholar
  24. 24.
    Quentin R, Martin C, Musser JM et al. Genetic characterization of a cryptic genospecies of Haemophilus causing urogenital and neonatal infections. J Clin Microbiol 1993; 31:1111–6.PubMedGoogle Scholar
  25. 25.
    Rosenau A, Sizaret PY, Musser JM et al. Adherence to human cells of a cryptic Haemophilus genospecies responsible for genital and neonatal infections. Infect Immun 1993; 61:4112–8.PubMedGoogle Scholar
  26. 26.
    Schafer H, Ewig S. Acute exacerbations in chronic obstructive pulmonary disease (COPD)—microbial patterns and risk factors. Monaldi Arch Chest Dis Oct; 2000; 55:415–9.Google Scholar
  27. 27.
    Gump DW, Phillips CA, Forsyth BR et al. Role of infection in chronic bronchitis. Am Rev Respir Dis 1976; 113:465–74.PubMedGoogle Scholar
  28. 28.
    Shann F. Etiology of severe pneumonia in children in developing countries. Pediatr Infect Dis 1986; 5:247–52.PubMedCrossRefGoogle Scholar
  29. 29.
    Weinberg GA, Ghafoor A, Ishaq Z et al. Clonal analysis of Hemophilus influenzae isolated from children from Pakistan with lower respiratory tract infections. J Infect Dis 1989; 160:634–43.PubMedCrossRefGoogle Scholar
  30. 30.
    Berk SL, Holtsclaw SA, Wiener SL et al. Nontypeable Haemophilus influenzae in the elderly. Arch Intern Med 1982; 142:537–9.PubMedCrossRefGoogle Scholar
  31. 31.
    Musher DM, Kubitschek KR, Crennan J et al. Pneumonia and acute febrile tracheobronchitis due to Haemophilus influenzae. Ann Int Med 1983; 99:444–450.PubMedGoogle Scholar
  32. 32.
    Wallace RJ, Jr, Musher DM, Septimus EJ et al. Haemophilus influenzae infections in adults: Characterization of strains by serotypes, biotypes, and β lactamase production. J Infect Dis 1981; 144:101–106.PubMedCrossRefGoogle Scholar
  33. 33.
    Deulofeu F, Nava JM, Bella F et al. Prospective epidemiological study of invasive Haemophilus influenzae disease in adults. Eur J Clin Microbiol Infect Dis 1994; 13:633–8.PubMedCrossRefGoogle Scholar
  34. 34.
    Bondy J, Berman S, Glazner J et al. Direct expenditures related to otitis media diagnoses: extrapolations from a pediatric medicaid cohort. Pediatrics 2000; 105:E72.PubMedCrossRefGoogle Scholar
  35. 35.
    Vital and Health Statistics Series 10, No. 200. In: National Center for Health Statistics, Center for Disease Control, USA, 1996.Google Scholar
  36. 36.
    Wilson R, Read R, Cole P. Interaction of Haemophilus influenzae with mucus, cilia, and respiratory epithelium. J Infect Dis 1992; 165(suppl 1):S100–102.PubMedCrossRefGoogle Scholar
  37. 37.
    Kubiet M, Ramphal R. Adhesion of nontypeable Haemophilus influenzae from blood and sputum to human tracheobronchial mucins and lactoferrin. Infect Immun 1995; 63:899–902.PubMedGoogle Scholar
  38. 38.
    Reddy MS, Bernstein JM, Murphy TF et al. Binding between outer membrane proteins of nontypeable Haemophilus influenzae and human nasopharyngeal mucin. Infect Immun 1996; 64:1477–1479.PubMedGoogle Scholar
  39. 39.
    Reddy MS, Murphy TF, Faden HS et al. Middle ear mucin glycoprotein: purification and interaction with nontypeable Haemophilus influenzae and Moraxella catarrhalis. Otolaryngol-Head Neck Surg 1997; 116:175–180.PubMedCrossRefGoogle Scholar
  40. 40.
    Geluk F, Eijk PP, van Ham SM et al. The fimbria gene cluster of nonencapsulated Haemophilus influenzae. Infect Immun 1998; 66:406–417.PubMedGoogle Scholar
  41. 41.
    Gilsdorf JR, Chang HY, McCrea KW et al. Comparison of hemagglutinating pili of Haemophilus influenzae type b with similar structures of nontypeable Haemophilus influenzae. Infect Immun 1992; 60:374–379.PubMedGoogle Scholar
  42. 42.
    Krasan GP, Cutter D, Block SL et al. Adhesin expression in matched nasopharyngeal and middle ear isolates of nontypeable Haemophilus influenzae from children with acute otitis media. Infect Immun 1999; 67:449–454.PubMedGoogle Scholar
  43. 43.
    van Alphen L, Broek Geelen-van der, Blaas L et al. Blocking of fimbria-mediated adherence of Haemophilus influenzae by sialyl gangliosides. Infect Immun 1991; 59:4473–4477.PubMedGoogle Scholar
  44. 44.
    van Ham SM, van Alphen L, Mooi FR et al. Contribution of the major and minor subunits to fimbria-mediatedadherence of Haemophilus influenzae to human epithelial cells and erythrocytes. Infect Immun 1995; 63:4883–9.PubMedGoogle Scholar
  45. 45.
    van Alphen L, Poole J, Geelen L et al. The erythrocyte and epithelial cell receptors for Haemophilus influenzae are expressed independently. Infect Immun 1987; 55:2355–8.PubMedGoogle Scholar
  46. 46.
    Barenkamp SJ, St Geme III JW. Identification of a second family of high-molecular-weight adhesion proteins expressed by nontypeable Haemophilus influenzae. Mol Microbiol 1996; 19:1215–1223.PubMedCrossRefGoogle Scholar
  47. 47.
    St Geme III JW, Morena MLdl, Falkow S. A Haemophilus influenzae IgA protease-like protein promotes intimate interaction with human epithelial cells. Mol Microbiol 1994; 14:217–233.CrossRefGoogle Scholar
  48. 48.
    Hendrixson DR, St Geme III JW. The Haemophilus influenzae Hap serine protease promotes adherence and microcolony formation, potentiated by a soluble host protein. Mol Cell 1998; 2:841–50.PubMedCrossRefGoogle Scholar
  49. 49.
    Prasadarao NV, Lysenko E, Wass CA et al. Opacity-associated protein A contributes to the binding of Haemophilus influenzae to chang epithelial cells. Infect Immun 1999; 67:4153–60.PubMedGoogle Scholar
  50. 50.
    Sirakova T, Kolattukudy PE, Murwin D et al. Role of fimbriae expressed by nontypeable Haemophilus influenzae in pathogensis of and protection against otitis media and relatedness of the fimbrin subunit to outer membrane protein A. Infect Immun 1994; 62:2002–2020.PubMedGoogle Scholar
  51. 51.
    Novotny LA, Jurcisek JA, Pichichero ME et al. Epitope mapping of the outer membrane protein P5-homologous fimbrin adhesin of nontypeable Haemophilus influenzae. Infect Immun 2000; 68:2119–2128.PubMedCrossRefGoogle Scholar
  52. 52.
    Barenkamp SJ, Leininger E. Cloning, expression and DNA sequence analysis of genes encoding nontypeable Haemophilus influenzae high-molecular-weight surface-exposed proteins related to hemagglutinin of Bordetella pertussis. Infect Immun 1992; 60:1302–1313.PubMedGoogle Scholar
  53. 53.
    St Geme III JW, Falkow S, Barenkamp SJ. High-molecular-weight proteins of nontypable Haemophilus influenzae mediate attachment to human epithelial cells. Proc Natl Acad Sciences USA 1993; 90:2875–2879.CrossRefGoogle Scholar
  54. 54.
    Hendrixson DR, de la Morena ML, Stathopoulos C et al. Structural determinants of processing and secretion of the Haemophilus influenzae hap protein. Mol Microbiol 1997; 23:505–18.CrossRefGoogle Scholar
  55. 55.
    St Geme III JW. Insights into the mechanism of respiroatory tract colonization by nontypeable Haemophilus influenzae. Pediatr Infect Dis J 1997; 116:931–935.Google Scholar
  56. 56.
    Weiser JN, Chong ST, Greenberg D et al. Identification and characterization of a cell envelope protein of Haemophilus influenzae contributing to phase variation in colony opacity and nasopharyngeal colonization. Mol Microbiol 1995; 17:555–64.PubMedCrossRefGoogle Scholar
  57. 57.
    Munson RS, Jr., Grass S, West R. Molecular cloning and sequence of the gene for outer membrane protein P5 of Haemophilus influenzae. Infect Immun 1993; 61:4017–4020.PubMedGoogle Scholar
  58. 58.
    Webb DC, Cripps AW. Secondary structure and molecular analysis of interstrain variability in the P5 outer-membrane protein of non-typable Haemophilus influenzae isolated from diverse anatomical sites. J Med Microbiol 1998; 47:1059–1067.PubMedCrossRefGoogle Scholar
  59. 59.
    Hill DJ, Toleman MA, Evans DJ et al. The variable P5 proteins of nontypeable Haemophilus influenzae target human CEACAM1. Mol Microbiol 2001; 39:850–862.PubMedCrossRefGoogle Scholar
  60. 60.
    Virji M, Evans D, Griffith J et al. Carcinoembryonic antigens are targeted by diverse strains of typable and non-typable Haemophilus influenzae. Mol Microbiol 2000; 36:784–95.PubMedCrossRefGoogle Scholar
  61. 61.
    St Geme III JW, Cutter D, Barenkamp SJ. Characterization of the genetic locus encoding Haemophilus influenzae type b surface fibrils. J Bacteriol 1996; 178:6281–7.Google Scholar
  62. 62.
    Barenkamp SJ, St Geme III JW. Identification of surface-exposed B-cell epitopes on high molecular-weight adhesion proteins of nontypeable Haemophilus influenzae. Infect Immun 1996; 64:3032–7.Google Scholar
  63. 63.
    St Geme III JW. Molecular determinants of the interaction between Haemophilus influenzae and human cells. Am. J. Respir. Crit Care Med 1996; 154:S192–S196.PubMedGoogle Scholar
  64. 64.
    St Geme III JW, Grass S. Secretion of the Haemophilus influenzae HMW1 and HMW2 adhesins involves a periplasmic intermediate and requires the HMWB and HMWC proteins. Mol Microbiol 1998; 27:617–630.CrossRefGoogle Scholar
  65. 65.
    St Geme III JW, Kumar W, Cutter D et al. Prevalence and distribution of the hmw and hia genes and the HMW and Hia adhesins among genetically diverse strains of nontypable Haemophilus influenzae. Infect Immun 1998; 66:364–8.Google Scholar
  66. 66.
    Noel GJ, Barenkamp SJ, III JWSG et al. High-molecular-weight surface-exposed proteins of Haemophilus influenzae mediate binding to macrophages. J Infect Dis 1994; 169:425–429.PubMedCrossRefGoogle Scholar
  67. 67.
    Gorter AD, Eijk PP, van Wettering S et al. Stimulation of the adherence of Haemophilus influenzae to human lung epithelial cells by antimicrobial neutrophil defensins. J Infect Dis 1998; 178:1067–1074.PubMedCrossRefGoogle Scholar
  68. 68.
    Noel GJ, Love DC, Mosser DM. High-molecular-weight proteins of nontypeable Haemophilus influenzae mediate bacterial adhesion to cellular proteoglycans. Infect Immun 1994; 62:4028–4033.PubMedGoogle Scholar
  69. 69.
    Moller LVM, Timens W, van der Bij W et al. Haemophilus influenzae in lung explants of patients with end-stage pulmonary disease. Am J Respir Critical Care Med 1998; 157(950–956).Google Scholar
  70. 70.
    Virkola R, Brummer M, Rauvala H et al. Interaction of fimbriae of Haemophilus influenzae type b with heparin-binding extracellular matrix proteins. Infect Immun 2000; 68:5696–5701.PubMedCrossRefGoogle Scholar
  71. 71.
    Lahteenmaki K, Virkola R, Pouttu R et al. Bacterial plasminogen receptors: in vitro evidence for a role in degradation of the mammalian extracellular matrix. Infect Immun 1995; 63:3659–64.PubMedGoogle Scholar
  72. 72.
    Khair OA, Davies RJ, Devalia JL. Bacterial-induced release of inflammatory mediators by bronchial epithelial cells. Eur Respir J 1996; 9:1913–1922.PubMedCrossRefGoogle Scholar
  73. 73.
    Clemans DL, R.J. Bauer, Hanson JA et al. Induction of proinflammatory cytokines from human respiratory epithelial cells after stimulation by nontypeable Haemophilus influenzae. Infect Immun 2000; 68:4430–4440.PubMedCrossRefGoogle Scholar
  74. 74.
    Tobias PS, Soldau K, Gegner JA et al. Lipopolysaccharide binding protein-mediated complexation of lipopolysaccharide with soluble CD14. J Biol Chem 1995; 270:10482–8.PubMedCrossRefGoogle Scholar
  75. 75.
    da Silva Correia J, Soldau K, Christen U et al. Lipopolysaccharide is in close proximity to each of the proteins in its membrane receptor complex. transfer from CD 14 to TLR4 and MD-2. J Biol Chem 2001; 276:21129–35.PubMedCrossRefGoogle Scholar
  76. 76.
    Swords WE, Buscher BA, ver Steeg Ii K et al. Nontypeable Haemophilus influenzae adhere to and invade human bronchial epithelial cells via an interacting of lipooligosaccharide with the PAF receptor. Mol Microbiol 2000; 37:13–27.PubMedCrossRefGoogle Scholar
  77. 77.
    Viriyakosol S, Tobias PS, Kitchens RL et al. MD-2 binds to bacterial lipopolysaccharide. J Biolog Chem 2001; 276:38044–51.Google Scholar
  78. 78.
    Klein JO. The burden of otitis media. Vaccine 2000; 19:S2–S8.PubMedCrossRefGoogle Scholar
  79. 79.
    Faden H. The microbiologic and immunologic basis for recurrent otitis media in children. Eur J Pediatr 2001; 160:407–413.PubMedCrossRefGoogle Scholar
  80. 80.
    Yamanaka N, Faden H. Local antibody response to P6 of nontypable Haemophilus influenzae in otitis-prone and normal children. Acta Otolaryngology 1993; 113:524–529.CrossRefGoogle Scholar
  81. 81.
    Kodama H, Faden H. Cellular immunity to the P6 outer membrane protein of nontypeable Haemophilus influenzae. Infect Immun 1995; 63:2467–2472.PubMedGoogle Scholar
  82. 82.
    Clancy RL, Cripps AW, Yeung S et al. Salivary and serum antibody responses to Haemophilus influenzae infection in Papua New Guinea. PNG Med J 1987; 30:271–276.Google Scholar
  83. 83.
    Shuto T, Xu H, Wang B et al. Activation of NF-kB by nontypeable Hemophilus influenzae is mediated by toll-like receptor 2-TAK1 -dependent NIK-IKK a /b-IkBa and MKK3/6-p38 MAP kinase signaling pathways in epithelial cells. Proc Nat Acad Sci USA 2001; 98:8774–8779.PubMedCrossRefGoogle Scholar
  84. 84.
    Hatada EN, Krappmann D, Scheidereit C. NF-kappaB and the innate immune response. Curr Opin Immunol 2000; 12:52–8.PubMedCrossRefGoogle Scholar
  85. 85.
    Foxwell AR, Kyd JM, Cripps AW. Nontypeable Haemophilus influenzae: pathogenesis and prevention. Microbiol Mol Biol Rev 1998; 62:294–308.PubMedGoogle Scholar
  86. 86.
    Maskell DJ, Szabo MJ, Butler PD et al. Molecular biology of phase-variable lipopolysaccharide biosynthesis by Haemophilus influenzae. J Infect Dis 1992; 165(Sl):S90–2.PubMedCrossRefGoogle Scholar
  87. 87.
    Lomholt H, van Alphen L, Kilian M. Antigenic variation of immunoglobulin A1 proteases among sequential isolates of Haemophilus influenzae from healthy children and patients with chronic obstructive pulmonary disease. Infect Immun 1993; 61:4575–4581.PubMedGoogle Scholar
  88. 88.
    Duim B, Dankert J, Jansen HM et al. Genetic analysis of the diversity in outer membrane P2 of non-encapsulated Haemophilus influenzae. Microbial Pathogenesis 1993; 14:451–462.PubMedCrossRefGoogle Scholar
  89. 89.
    Wallace FJ, Clancy RL, Cripps AW. An animal model demonstration of enhanced clearance of nontypable Haemophilus influenzae from respiratory tract after antigen stimulation of gut-associated lymphoid tissue. Am Rev Respir Dis 1989; 140:311–316.PubMedCrossRefGoogle Scholar
  90. 90.
    Kyd JM, Dunkley ML, Cripps AW. Enhanced respiratory clearance of nontypeable Haemophilus influenzae following mucosal immunization with P6 in a rat model. Infect Immun 1995; 63:2931–2940.PubMedGoogle Scholar
  91. 91.
    Magnuson K, Hermansson A, Melhus A et al. The tympanic membrane and middle ear mucosa during non-typeable Haemophilus influenzae and Haemophilus influenzae type b acute otitis media: a study in the rat. Acta Otolaryngology 1997; 117:396–405.CrossRefGoogle Scholar
  92. 92.
    Giebink GS. Otitis media: the chinchilla model. Microbial Drug Resist 1999; 5:57–72.CrossRefGoogle Scholar
  93. 93.
    Fleischmann RD, Adams MD, White O et al. Whole-genome random sequencing and assembley of Haemophilus influenzae Rd. Science 1995; 269:496–512.PubMedCrossRefGoogle Scholar
  94. 94.
    Kyd J, Cripps A. Identifying vaccine antigens and assessing delivery systems for the prevention of bacterial infections. J Biotechnol 2000; 83:85–90.PubMedCrossRefGoogle Scholar
  95. 95.
    Poolman JT, Bakaletz L, Cripps A et al. Developing a nontypeable Haemophilus influenzae (NTHi) vaccine. Vaccine 2000; 19(S1):S108 – S115.PubMedGoogle Scholar
  96. 96.
    Clancy RL, Cripps AW, Muree-Allen K et al. Oral immunisation with killed Haemophilus influenzae for protection against acute bronchitis in chronic obstructive pulmonary disease. Lancet 1985; ii:1395–1397.Google Scholar
  97. 97.
    Clancy R, Cripps A, Pang G et al. The paradox of immunisation against Haemophilus influenzae-related endobronchitis: protection restricted to ingestion of “non adjuvenated” vaccine. In: Mestecky J, McGhee J, eds. Recent Advances in Mucosal Immunology. Vol. 216B. New York: Plenum Press, 1987:1759–1764.Google Scholar
  98. 98.
    Clancy RL, Cripps AW, Gebeski V. Protection against recurrent acute bronchitis after oral immunization with killed Haemophilus influenzae. Med J Aust 1990; 152:413–416.PubMedGoogle Scholar
  99. 99.
    Clancy RL, Cripps AW. Specific protection against acute bronchitis associated with nontypeable Haemophilus influenzae. J Infect Dis 1992; 165(suppl 1):S194–S195.PubMedCrossRefGoogle Scholar
  100. 100.
    Lehmann D, Coakley KJ, Coakley CA et al. Reduction in the incidence of acute bronchitis by an oral Haemophilus influenzae vaccine in patients with chronic bronchitis in the highlands of Papua New Guinea. Am Rev Respir Dis 1991; 144:324–330.PubMedCrossRefGoogle Scholar
  101. 101.
    Clancy RL, Pang G, Dunkley G et al. Control of bacterial colonisation of the respiratory tract mucosa in man. In: Husband AJ, Beagley KW, Clancy RL et al eds. Mucosal Solutions: Advances in mucosal immunology. Vol I. Sydney: University of Sydney, 1997:261–268.Google Scholar
  102. 102.
    Tandon MK, Gebski V. A controlled trial of a killed Haemophilus influenzae vaccine for prevention of acute exacerbations of chronic bronchitis. Aust NZ J Medicine 1991; 21:427–432.CrossRefGoogle Scholar
  103. 103.
    Foxwell AR, Cripps AW. Haemophilus influenzae oral vaccination against acute bronchitis. Cochrane Database Syst Rev 2000; 2:CD001958.PubMedGoogle Scholar
  104. 104.
    Gutiérrez-Tarango MD, Berber A. Efficacy of a bacterial extract (OM-85 BV) in preventing recurrent respiratory tract infections in susceptible children. Clin Drug Invest 1997; 13:76–84.CrossRefGoogle Scholar
  105. 105.
    Gutiérrez-Tarango MD, Berber A. Safety and efficacy of two courses of OM-85 BV in the prevention of respiratory tract infections in children during 12 months. Chest 2001; 119:1742–48.PubMedCrossRefGoogle Scholar
  106. 106.
    Orcel B, Delclaux B, Baud M et al. Oral immunization with bacterial extracts for protection against acute bronchitis in elderly institutionalized patients with chronic bronchitis. Eur Respir J 1994; 7:446–452.PubMedCrossRefGoogle Scholar
  107. 107.
    Collet JP, Shapiro S, Ernst P et al. Effects of an immunostimulating agent on acute exacerbations and hospitalizations in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1997; 156:1719–1724.PubMedGoogle Scholar
  108. 108.
    Heintz B, Schlenter WW, Kirsten R et al. Clinical efficacy of Broncho-Vaxom® in adult patients with chronic purulent sinusitis—a multicentric, placebo-controlled, double-blind study. Int J Clin Pharmacol Ther Toxicol 1989; 27:530–534.PubMedGoogle Scholar
  109. 109.
    Foxwell AR, Kyd JM, Karupiah G et al. CD8+ T cells have an essential role in pulmonary clearance of nontypeable Haemophilus influenzae following mucosal immunisation. Infect Immun 2001; 69:2636–2642.PubMedCrossRefGoogle Scholar
  110. 110.
    Wallace FJ, Cripps AW, Clancy RL et al. A role for intestinal T lymphocytes in bronchus mucosal immunity. Immunol 1991; 74:68–73.Google Scholar
  111. 111.
    Kyd JM, Cripps AW. Nontypeable Haemophilus influenzae: Challenges in developing a vaccine. J Biotechnol 1999; 73:103–108.PubMedCrossRefGoogle Scholar
  112. 112.
    Kyd JM, Cripps AW. Potential of a novel protein, OMP26, from nontypeable Haemophilus influenzae to enhance pulmonary clearance in a rat model. Infect Immun 1998; 66:2272–2278.PubMedGoogle Scholar
  113. 113.
    Bowman LM, Holt PG. Selective enhancement of systemic Thuimmunity in immunologically immature rats with an orally administered bacterial extract. Infect Immun 2001; 69:3719–3727.PubMedCrossRefGoogle Scholar
  114. 114.
    Pang GT, Yeung S, Clancy RL et al. Induction of antigen-reactive and IL-2 receptor bearing cells following oral immunisation in humans. In: Mestecky J, McGhee J, eds. Recent Advances in Mucosal Immunology. Vol 216B. New York: Plenum Press, 1987: 1731–1739.Google Scholar
  115. 115.
    Wallace FJ, Witt CS, Clancy RL et al. Protection against non-typeable Haemophilus influenzae following sensitization of gut associated lymphoid tissue: Role of specific antibody and phagocytes. Immunol Cell Biol 1995; 73:258–265.PubMedCrossRefGoogle Scholar
  116. 116.
    Hansen EJ, Hart DA, McGehee JL et al. Immune enhancement of pulmonary clearance of nontypable Haemophilus influenzae. Infect Immun 1988; 56:182–190.PubMedGoogle Scholar
  117. 117.
    Bosch A, Lucena F, Pares R et al. Bacterial immunostimulant (Broncho-Vaxom) versus levamisole on the humoral immune response in mice. J Immunopharm 1983; 5:107–116.CrossRefGoogle Scholar
  118. 118.
    Puigdollers JM, Rodes Serna G, Hernandez del Rey L et al. Immunoglobulin production in man stimulated by an orally administered bacterial lysate. Respiration 1980; 40:142–149.PubMedCrossRefGoogle Scholar
  119. 119.
    Clancy RL, Cripps AW, Husband AJ et al. Specific immune response in the respiratory tract after administration of an oral polyvalent bacterial vaccine. Infect Immun 1983; 39:491–6.PubMedGoogle Scholar
  120. 120.
    Cripps AW, Clancy RL, Murree-Allen K et al. Quantitation of isotype specific Haemophilus influenzae antibody in serum and saliva of normal subjects and chronic bronchitis. Asian Pac J Allergy Immunol 1986; 4:5–11.PubMedGoogle Scholar
  121. 121.
    Anthonisen NR. OM-85 BV for COPD. Am J Respir Crit Care Med 1997; 156:1713–1714.PubMedGoogle Scholar
  122. 122.
    Ekberg-Jansson A, Larrson S, Löfdahl C-G. Preventing exacerbations on chronic bronchitis and COPD. BMJ 2001; 322:1259-1260.PubMedCrossRefGoogle Scholar
  123. 123.
    Loeb MR, Smith DH. Outer membrane protein composition in disease isolates of Haemophilus influenzae: pathogenic and epidemiological implications. Infect Immun 1980; 30:709–717.PubMedGoogle Scholar
  124. 124.
    Nelson MB, Munson RS Jr, Apicella MA et al. Molecular conservation of the P6 outer membrane among strains of Haemophilus influenzae: analysis of antigenic determinants, gene sequences, and restriction fragment length polymorphisms. Infect Immun 1991; 59:2658–2663.PubMedGoogle Scholar
  125. 125.
    Green BA, Farley JE, Quinn-Dey T et al. The e (P4) outer membrane protein of Haemophilus influenzae: Biologic activity of anti-e serum and cloning and sequencing of the structural gene. Infect Immun 1991; 59:3191–3198.PubMedGoogle Scholar
  126. 126.
    Akkoyunlu M, Ruan M, Forsgren A. Distribution of Protein D, an immunoglobulin D-binding protein in Haemophilus strains. Infect Immun 1991; 59:1231–1238.PubMedGoogle Scholar
  127. 127.
    Haase EM, Yi K, Morse GD et al. Mapping of bactericidal epitopes on the P2 porin protein of nontypeable Haemophilus influenzae. Infect Immun 1994; 62:3712–3722.PubMedGoogle Scholar
  128. 128.
    Gu XX, Sun J, Jin S et al. Detoxified lipooligosaccharide from nontypeable Haemophilus influenzae conjugated to proteins confers protection against otitis media in chinchillas. Infect Immun 1997; 65:4488–93.PubMedGoogle Scholar
  129. 129.
    Barenkamp SJ. Immunization with high-molecluar-weight adhesion proteins of nontypeable Haemophilus influenzae modifies experimental otitis media in chinchillas. Infect Immun 1996; 64:1246–1251.PubMedGoogle Scholar
  130. 130.
    El-Adhami W, Kyd JM, Bastin DA et al. Characterisation of the gene for OMP26 from nontypeable Haemophilus influenzae and immune responses to the recombinant protein. Infect Immun 1999; 67:1935–1942.PubMedGoogle Scholar
  131. 131.
    Kyd JM, Cripps AW. Towards a protein vaccine for nontypeable Haemophilus influenzae. Clin Infect Dis 1999; 28:238.PubMedCrossRefGoogle Scholar
  132. 132.
    Bakaletz LO, Leake ER, Billy JM et al. Relative immunogenicity and efficacy of two synthetic chimetic peptides of fimbrin as vaccinogens against nasopharyngeal colonization by nontypeable Haemophilus influenzae in the chinchilla. Vaccine 1997; 15:955–961.PubMedCrossRefGoogle Scholar
  133. 133.
    Webb DC, Cripps AW. A P5 peptide that is homologous to peptide 10 of OprF from Pseudomonas aeruginosa enhances clearance of nontypeable Haemophilus influenzae from acutely infected rat lung in the absence of detectable peptide-specific antibody. Infect Immun 2000; 68:377–381.PubMedCrossRefGoogle Scholar
  134. 134.
    Bakaletz LO, Kennedy B-J, Novotny LA et al. Protection against development of otitis media induced by nontypeable Haemophilus influenzae by both active and passive immunization in a chinchilla model of virus-bacterium infection. Infect Immun 1999; 67:2746–2762.PubMedGoogle Scholar
  135. 135.
    Kennedy B-J, Novotny LA, Jurcisek JA et al. Passive transfer of antiserum specific for immunogens derived from a nontypeable Haemophilus influenzae adhesin and lipoprotein D prevents otitis media after heterologous challenge. Infect Immun 2000; 68:2756–2765.PubMedCrossRefGoogle Scholar
  136. 136.
    Janson H, Heden LO, Forsgren A. Protein D, the immunoglobulin D-binding protein of Haemophilus influenzae, is a lipoprotein. Infect Immun 1992; 60:1336–1342.PubMedGoogle Scholar
  137. 137.
    Song X-M, Forsgren A, Janson H. The gene encoding protein D (hyp) is highly conserved among Haemophilus influenzae type b and nontypeable strains. Infect Immun 1995; 63:696–699.PubMedGoogle Scholar
  138. 138.
    Akkoyunlu M, Melhus A, Capiau C et al. The acylated form of protein D of Haemophilus influenzae is more immunogenic than the non-acylated form and elicits an adjuvant effect when it is used as a carrier conjugated to polyribosyl ribitol phosphate. Infect Immun 1997; 65:5010–5016.PubMedGoogle Scholar
  139. 139.
    Murphy TF, Bartos LC, Rice PA et al. Identification of a 16,600-Dalton outer membrane protein on nontypable Haemophilus influenzae as a target for human serum bactericidal antibody. J Clin Invest 1986; 78:1020–1027.PubMedCrossRefGoogle Scholar
  140. 140.
    DeMaria TF, Urwin DM, Leake ER. Immunization with outer membrane protein P6 from nontypeable Haemophilus influenzae induces bactericidal antibody and affords protection in the chinchilla model of otitis media. Infect Immun 1996; 64:5187–5192.PubMedGoogle Scholar
  141. 141.
    Green BA, Vazquez ME, Zlotnick GW et al. Evaluation of mixtures of purified Haemophilus influenzae outer membrane proteins in protection against challenge with nontypable H. influenzae in the chinchilla otitis media model. Infect Immun 1993; 61:1950–1957.PubMedGoogle Scholar
  142. 142.
    Sabirov A, Kodama S, Hirano T et al. Intranasal immunization enhances clearance of nontypeable Haemophilus influenzae and reduces stimulation of tumor necrosis factor alpha production in the murine model of otitis media. Infect Immun 2001; 69:2964–2971.PubMedCrossRefGoogle Scholar
  143. 143.
    Kimura A, Hansen EJ. Antigenic and phenotypic variation of Haemophilus influenzae type b lipooligosaccharide and their relationship to virulence. Infect Immun 1986; 51:69–79.PubMedGoogle Scholar
  144. 144.
    Weiser JN, Williams, Moxon ER. Phase-variable lipopolysaccharide structures enhance the invasive capacity of Haemophilus influenzae. Infect Immun 1990; 58:3455–3457.PubMedGoogle Scholar
  145. 145.
    Weiser JN, Pan N, McGowan KL et al. Phosphorylcholine on the lipopolysaccharide of Haemophilus influenzae contributes to persistence in the respiratory tract and sensitivity to serum killing mediated by C-reactive protein. J Exp Med 1998; 187:631–40.PubMedCrossRefGoogle Scholar
  146. 146.
    Wu TH, Gu XX. Outer membrane proteins as a carrier for detoxified lipooligosaccharide conjugate vaccines for nontypeable Haemophilus influenzae. Infect Immun 1999; 67:5508–5513.PubMedGoogle Scholar
  147. 147.
    Sun J, Chen J, Cheng Z et al. Biological activities of antibodies elicited by lipooligosaccharide based-conjugate vaccines of nontypeable Haemophilus influenzae in an otitis media model. Vaccine 2000; 18:1264–1272.PubMedCrossRefGoogle Scholar
  148. 148.
    Kyd JM, Cripps AW. Modulation of antigen-specific T and B cell responses influence bacterial clearance of nontypeable Haemophilus influenzae from the lung in a rat model. Vaccine 1996; 14:1471–1478.PubMedCrossRefGoogle Scholar
  149. 149.
    Neary JM, Yi KY, Karalus RJ et al. Antibodies to loop 6 of the P2 porin protein of nontypeable Haemophilus influenzae are bactericidal against multiple strains. Infect Immun 2001; 69:773–778.PubMedCrossRefGoogle Scholar
  150. 150.
    Webb DC, Cripps AW. Immunization with recombinant transferrin binding protein B enhances clearance of nontypeable Haemophilus influenzae from the rat lung. Infect Immun 1999; 67:2138–2144.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2003

Authors and Affiliations

  • Allan W. Cripps
  • Jennelle M. Kyd

There are no affiliations available

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