title: No long-term evidence of hyporesponsiveness after use of pneumococcal conjugate vaccine in children previously immunized with pneumococcal polysaccharide vaccine.
abstract: A randomized controlled trial in Fiji examined the immunogenicity and effect on nasopharyngeal carriage after 0, 1, 2, or 3 doses of 7-valent pneumococcal conjugate vaccine (PCV7; Prevnar) in infancy followed by 23-valent pneumococcal polysaccharide vaccine (23vPPV; Pneumovax) at 12 months of age. At 18 months of age, children given 23vPPV exhibited immune hyporesponsiveness to a micro-23vPPV (20%) challenge dose in terms of serotype-specific IgG and opsonophagocytosis, while 23vPPV had no effect on vaccine-type carriage.
  
  
  
  This follow-up study examined the long-term effect of the 12-month 23vPPV dose by evaluating the immune response to 13-valent pneumococcal conjugate vaccine (PCV13) administration 4 to 5 years later.
  
  
  
  Blood samples from 194 children (now 5-7 years old) were taken before and 28 days after PCV13 booster immunization. Nasopharyngeal swabs were taken before PCV13 immunization. We measured levels of serotype-specific IgG to all 13 vaccine serotypes, opsonophagocytosis for 8 vaccine serotypes, and memory B-cell responses for 18 serotypes before and after PCV13 immunization.
  
  
  
  Paired samples were obtained from 185 children. There were no significant differences in the serotype-specific IgG, opsonophagocytosis, or memory B-cell response at either time point between children who did or did not receive 23vPPV at 12 months of age. Nasopharyngeal carriage of PCV7 and 23vPPV serotypes was similar among the groups. Priming with 1, 2, or 3 PCV7 doses during infancy did not affect serotype-specific immunity or carriage.
  
  
  
  Immune hyporesponsiveness induced by 23vPPV in toddlers does not appear to be sustained among preschool children in this context and does not affect the pneumococcal carriage rate in this age group.
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia. Electronic address: paul.licciardi@mcri.edu.au.
authors.forename: Paul V
authors.initials: PV
authors.lastname: Licciardi
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: Zheng Quan
authors.initials: ZQ
authors.lastname: Toh
authors.affiliation: Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Clutterbuck
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: Anne
authors.initials: A
authors.lastname: Balloch
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: Rachel A
authors.initials: RA
authors.lastname: Marimla
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: Leena
authors.initials: L
authors.lastname: Tikkanen
authors.affiliation: Department of Paediatrics, University of Melbourne, Parkville, Australia; Clinical Epidemiology and Biostatistics Unit, Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: Karen E
authors.initials: KE
authors.lastname: Lamb
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: Kathryn J
authors.initials: KJ
authors.lastname: Bright
authors.affiliation: Mataika House, National Centre for Communicable Disease Research, Suva, Fiji.
authors.forename: Uraia
authors.initials: U
authors.lastname: Rabuatoka
authors.affiliation: Colonial War Memorial Hospital, Suva, Fiji.
authors.forename: Lisi
authors.initials: L
authors.lastname: Tikoduadua
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia.
authors.forename: Laura K
authors.initials: LK
authors.lastname: Boelsen
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: Eileen M
authors.initials: EM
authors.lastname: Dunne
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne, Australia; Department of Paediatrics, University of Melbourne, Parkville, Australia; Department of Microbiology and Immunology at the Peter Doherty Institute for Infection and Immunity, University of Melbourne, Parkville, Australia.
authors.forename: Catherine
authors.initials: C
authors.lastname: Satzke
authors.affiliation: Center for Quantitative Medicine, Duke-NUS Graduate Medical School, Singapore; Department of International Health, University of Tampere, Tampere, Finland.
authors.forename: Yin Bun
authors.initials: YB
authors.lastname: Cheung
authors.affiliation: Department of Paediatrics, University of Oxford, and the NIHR Oxford Biomedical Research Centre, Oxford, United Kingdom.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Pollard
authors.affiliation: Department of Paediatrics, University of Melbourne, Parkville, Australia; Centre for International Child Health, Murdoch Childrens Research Institute, Melbourne, Australia.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Russell
authors.affiliation: Pneumococcal Research, Murdoch Childrens Research Institute, Melbourne, Australia; Menzies School of Health Research, Darwin, Australia; London School of Hygiene and Tropical Medicine, London, United Kingdom.
authors.forename: Edward K
authors.initials: EK
authors.lastname: Mulholland
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005367:Fiji; D005500:Follow-Up Studies; D000069443:Heptavalent Pneumococcal Conjugate Vaccine / Q000008:administration & dosage / Q000276:immunology; D006760:Hospitalization; D006801:Humans; D007109:Immunity; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011008:Pneumococcal Infections / Q000276:immunology* / Q000517:prevention & control*; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D013296:Streptococcus pneumoniae / Q000276:immunology*; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000276:immunology*
chemical_list: C414006:23-valent pneumococcal capsular polysaccharide vaccine; D000907:Antibodies, Bacterial; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D007074:Immunoglobulin G; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate
keywords: 23vPPV; Pneumococcal polysaccharide vaccine; antibody; hyporesponsiveness; memory B cell; opsonophagocytosis
references.citation: Vaccine. 2010 Feb 3;28(5):1333-40
references.pmid: 19932671
references.citation: Vaccine. 2014 Jan 9;32(3):417-24
references.pmid: 24300594
references.citation: Vaccine. 2010 Apr 19;28(18):3086-94
references.pmid: 20199764
references.citation: J Infect Dis. 2012 Feb 1;205(3):422-30
references.pmid: 22158565
references.citation: Lancet Infect Dis. 2007 Sep;7(9):597-606
references.pmid: 17714673
references.citation: MMWR Recomm Rep. 1997 Apr 4;46(RR-8):1-24
references.pmid: 9132580
references.citation: Clin Infect Dis. 2011 Mar 15;52(6):736-42
references.pmid: 21367726
references.citation: Vaccine. 2012 Nov 6;30(48):6802-8
references.pmid: 23000122
references.citation: Commun Dis Intell Q Rep. 2013 Mar 31;37(1):E21-39
references.pmid: 23692156
references.citation: Lancet. 1986 Oct 18;2(8512):877-81
references.pmid: 2876325
references.citation: Vaccine. 1991 Jun;9(6):403-7
references.pmid: 1887670
references.citation: Vaccine. 2013 Aug 2;31(35):3594-602
references.pmid: 23688525
references.citation: Cochrane Database Syst Rev. 2013 Jan 31;(1):CD000422
references.pmid: 23440780
references.citation: Vaccine. 2010 Mar 8;28(11):2296-301
references.pmid: 20116468
references.citation: PLoS One. 2013 Sep 12;8(9):e72588
references.pmid: 24069152
references.citation: Cold Spring Harb Perspect Med. 2013 Jul 01;3(7):
references.pmid: 23818515
references.citation: Expert Rev Vaccines. 2011 Mar;10(3):307-22
references.pmid: 21434799
references.citation: Clin Vaccine Immunol. 2008 Feb;15(2):182-93
references.pmid: 18032593
references.citation: Vaccine. 2000 Dec 8;19(9-10):1129-32
references.pmid: 11137248
references.citation: Clin Vaccine Immunol. 2006 Sep;13(9):1004-9
references.pmid: 16960111
references.citation: Vaccine. 2013 Dec 17;32(1):165-79
references.pmid: 24331112
references.citation: Lancet. 2009 Sep 12;374(9693):893-902
references.pmid: 19748398
references.citation: Vaccine. 2012 Jul 6;30(32):4717-8
references.pmid: 22621828
references.citation: J Infect. 2014 Oct;69(4):309-25
references.pmid: 24968238
references.citation: J Infect Dis. 2012 May 1;205(9):1408-16
references.pmid: 22457293
references.citation: Pediatr Infect Dis J. 2007 Aug;26(8):716-22
references.pmid: 17848884
references.citation: Vaccine. 2010 Apr 26;28(19):3341-9
references.pmid: 20206670
references.citation: Clin Vaccine Immunol. 2010 Dec;17(12):1970-6
references.pmid: 20943882
references.citation: Hum Vaccin. 2011 Sep;7(9):919-28
references.pmid: 21860256
references.citation: Clin Infect Dis. 2010 Apr 1;50(7):970-8
references.pmid: 20192729
references.citation: J Infect Dis. 2010 Feb 15;201(4):525-33
references.pmid: 20088694