Australian Aboriginal Children with Otitis Media Have Reduced Antibody Titers to Specific Nontypeable Haemophilus influenzae Vaccine Antigens.

Ruth B Thornton, Lea-Ann S Kirkham, Karli J Corscadden, Selma P Wiertsema, Angela Fuery, B Jan Jones, Harvey L Coates, Shyan Vijayasekaran, Guicheng Zhang, Anthony Keil, Peter C Richmond
Author Information
  1. Ruth B Thornton: School of Paediatrics and Child Health, The University of Western Australia, Perth, Western Australia, Australia ruth.thornton@uwa.edu.au.
  2. Lea-Ann S Kirkham: School of Paediatrics and Child Health, The University of Western Australia, Perth, Western Australia, Australia.
  3. Karli J Corscadden: School of Paediatrics and Child Health, The University of Western Australia, Perth, Western Australia, Australia.
  4. Selma P Wiertsema: School of Paediatrics and Child Health, The University of Western Australia, Perth, Western Australia, Australia.
  5. Angela Fuery: School of Paediatrics and Child Health, The University of Western Australia, Perth, Western Australia, Australia.
  6. B Jan Jones: School of Paediatrics and Child Health, The University of Western Australia, Perth, Western Australia, Australia.
  7. Harvey L Coates: School of Paediatrics and Child Health, The University of Western Australia, Perth, Western Australia, Australia.
  8. Shyan Vijayasekaran: School of Paediatrics and Child Health, The University of Western Australia, Perth, Western Australia, Australia.
  9. Guicheng Zhang: School of Paediatrics and Child Health, The University of Western Australia, Perth, Western Australia, Australia.
  10. Anthony Keil: PathWest Laboratory Medicine WA, Princess Margaret Hospital for Children, Subiaco, Western Australia, Australia.
  11. Peter C Richmond: School of Paediatrics and Child Health, The University of Western Australia, Perth, Western Australia, Australia.

Abstract

Indigenous populations experience high rates of otitis media (OM), with increased chronicity and severity, compared to those experienced by their nonindigenous counterparts. Data on immune responses to otopathogenic bacteria in these high-risk populations are lacking. Nontypeable (NTHi) is the predominant otopathogen in Australia. No vaccines are currently licensed to target NTHi; however, protein D (PD) from NTHi is included as a carrier protein in the 10-valent pneumococcal polysaccharide conjugate vaccine (PHiD10-CV), and other promising protein vaccine candidates exist, including outer membrane protein 4 (P4) and protein 6 (P6). We measured the levels of serum and salivary IgA and IgG against PD, P4, and P6 in Aboriginal and non-Aboriginal children with chronic OM who were undergoing surgery and compared the levels with those in healthy non-Aboriginal children (controls). We found that Aboriginal cases had lower serum IgG titers to all NTHi proteins assessed, particularly PD. In contrast, serum IgA and salivary IgA and IgG titers to each of these 3 proteins were equivalent to or higher than those in both non-Aboriginal cases and healthy controls. While serum antibody levels increased with age in healthy controls, no changes in titers were observed with age in non-Aboriginal cases, and a trend toward decreasing titers with age was observed in Aboriginal cases. This suggests that decreased serum IgG responses to NTHi outer membrane proteins may contribute to the development of chronic and severe OM in Australian Aboriginal children and other indigenous populations. These data are important for understanding the potential benefits of PHiD10-CV implementation and the development of NTHi protein-based vaccines for indigenous populations.

Keywords

References

  1. Vaccine. 2015 Jan 3;33(2):321-6 [PMID: 25448103]
  2. BMC Pediatr. 2008 Jun 02;8:23 [PMID: 18513453]
  3. Int J Pediatr Otorhinolaryngol. 2017 Jan;92 :119-125 [PMID: 28012512]
  4. J Infect Dis. 2000 Oct;182(4):1146-52 [PMID: 10979911]
  5. Vaccine. 1998 Dec;16(20):1950-6 [PMID: 9796049]
  6. Med J Aust. 2009 Nov 2;191(9 Suppl):S69-72 [PMID: 19883361]
  7. Vaccine. 2009 Dec 10;28(1):71-8 [PMID: 19818722]
  8. BMC Pediatr. 2015 Oct 19;15:162 [PMID: 26482232]
  9. Pediatr Infect Dis J. 2001 May;20(5):482-7 [PMID: 11368104]
  10. Vaccine. 2012 Feb 8;30(7):1235-8 [PMID: 22230580]
  11. J Infect Dis. 2016 Jan 15;213(2):314-23 [PMID: 26153407]
  12. Med J Aust. 2009 Nov 2;191(9 Suppl):S39-43 [PMID: 19883355]
  13. BMC Genomics. 2015 Aug 27;16:641 [PMID: 26311542]
  14. Med J Aust. 2009 Nov 2;191(9 Suppl):S60-4 [PMID: 19883359]
  15. Vaccine. 2004 Sep 3;22(25-26):3449-56 [PMID: 15308371]
  16. Hum Biol. 2015 Apr;87(2):92-108 [PMID: 26829293]
  17. BMC Pediatr. 2014 Aug 11;14:200 [PMID: 25109288]
  18. Lancet. 2006 Mar 4;367(9512):740-8 [PMID: 16517274]
  19. Vaccine. 2011 Jul 18;29(32):5163-70 [PMID: 21621576]
  20. J Pediatr. 1993 Feb;122(2):212-8 [PMID: 8429433]
  21. Hum Vaccin Immunother. 2012 Jun;8(6):799-805 [PMID: 22495112]
  22. Vaccine. 2011 Jan 29;29(5):1023-8 [PMID: 21129398]
  23. Vaccine. 2005 Jan 26;23(10):1294-300 [PMID: 15652672]
  24. Pediatr Infect Dis J. 1994 Nov;13(11):983-9 [PMID: 7845752]
  25. BMC Ear Nose Throat Disord. 2013 Oct 08;13(1):12 [PMID: 24099576]
  26. J Clin Microbiol. 2016 Sep;54(9):2380-3 [PMID: 27335148]
  27. PLoS Med. 2014 Jun 03;11(6):e1001657 [PMID: 24892763]
  28. APMIS. 1996 Oct;104(10):709-17 [PMID: 8980621]
  29. BMC Pediatr. 2009 Feb 19;9:14 [PMID: 19228431]
  30. Lancet Infect Dis. 2016 Apr;16(4):480-92 [PMID: 27036355]
  31. Vaccine. 2011 Feb 1;29(6):1211-21 [PMID: 21167861]
  32. Pediatr Infect Dis J. 2011 Aug;30(8):645-50 [PMID: 21487325]
  33. Pediatr Infect Dis J. 2007 May;26(5):447-9 [PMID: 17468659]
  34. Clin Vaccine Immunol. 2014 Feb;21(2):250-2 [PMID: 24285816]
  35. Infect Immun. 2001 May;69(5):2964-71 [PMID: 11292713]
  36. Infect Immun. 1996 Dec;64(12):5187-92 [PMID: 8945564]
  37. Vaccine. 2010 Oct 18;28(44):7184-92 [PMID: 20800701]
  38. Vaccine. 2004 Aug 13;22(23-24):3112-21 [PMID: 15297063]
  39. Acta Otolaryngol. 1995 Nov;115(6):796-803 [PMID: 8749202]
  40. Ann Otol Rhinol Laryngol. 1995 Jul;104(7):542-9 [PMID: 7598367]
  41. Med J Aust. 2009 May 18;190(10):598-600 [PMID: 19450214]
  42. Pediatr Infect Dis J. 2006 Sep;25(9):782-90 [PMID: 16940834]
  43. J Infect Dis. 2007 Nov 15;196(10):1528-36 [PMID: 18008233]
  44. Clin Vaccine Immunol. 2015 Dec 16;23 (2):155-61 [PMID: 26677200]
  45. BMC Pediatr. 2005 Jul 20;5:27 [PMID: 16033643]
  46. PLoS One. 2012;7(11):e49061 [PMID: 23152850]
  47. Int J Pediatr Otorhinolaryngol. 2008 Jan;72(1):57-61 [PMID: 18006084]
  48. Infect Immun. 2008 Oct;76(10):4546-53 [PMID: 18644877]
  49. J Pediatric Infect Dis Soc. 2016 Sep;5(3):237-48 [PMID: 27125273]
  50. Microbiol Immunol. 2011 Aug;55(8):574-81 [PMID: 21605159]

MeSH Term

Adolescent
Antibodies, Bacterial
Australia
Child
Child, Preschool
Female
Haemophilus Vaccines
Haemophilus influenzae
Humans
Immunoglobulin A
Immunoglobulin G
Infant
Male
Otitis Media
Surveys and Questionnaires

Chemicals

Antibodies, Bacterial
Haemophilus Vaccines
Immunoglobulin A
Immunoglobulin G

Word Cloud

Created with Highcharts 10.0.0NTHiAboriginalproteinserumpopulationsIgGnon-AboriginalcasestitersOMvaccinesPDlevelsIgAchildrenhealthycontrolsproteinsageAustralianindigenousincreasedcomparedresponsesNontypeablevaccinePHiD10-CVoutermembraneP4P6salivarychronicantibodyobserveddevelopmentHaemophilusinfluenzaeIndigenousexperiencehighratesotitismediachronicityseverityexperiencednonindigenouscounterpartsDataimmuneotopathogenicbacteriahigh-risklackingpredominantotopathogenAustraliacurrentlylicensedtargethoweverDincludedcarrier10-valentpneumococcalpolysaccharideconjugatepromisingcandidatesexistincluding46measuredundergoingsurgeryfoundlowerassessedparticularlycontrast3equivalenthigherchangestrendtowarddecreasingsuggestsdecreasedmaycontributeseveredataimportantunderstandingpotentialbenefitsimplementationprotein-basedChildrenOtitisMediaReducedAntibodyTitersSpecificVaccineAntigensnontypeable

Similar Articles

Cited By