title: Modeling pneumococcal nasopharyngeal acquisition as a function of anticapsular serum antibody concentrations after pneumococcal conjugate vaccine administration.
abstract: A prior 7- and 13-valent pneumococcal conjugate vaccine (PCV7 and PCV13) study provided sufficient data (N=1754; Jewish, n=1154; Bedouin, n=595; other, n=5) to investigate the association between nasopharyngeal (NP) acquisition of common PCV7 serotypes and cross-reacting 6A (PCV7+6A) and IgG concentrations.
  
  
  
  Using a logistic regression model, serotype specific association between postinfant series IgG concentration (age 7months) and new NP acquisition between ages 7 and 24months was assessed and adjusted for ethnicity. From a subset of subjects with new NP acquisition (n=9-152 across serotypes studied), new acquisition percentiles and associated IgG concentrations were calculated.
  
  
  
  For the serotypes studied, new NP acquisition rates decreased as IgG concentrations increased. Ethnicity did not influence these associations despite differences in carriage rates. From the subset with new acquisitions, 50% of the events occurred at IgG concentrations >0.61-5.58μg/mL; and 10% of the acquisitions occurred at IgG concentrations >2.48-17.69μg/mL.
  
  
  
  Remarkably high IgG concentrations are required to reduce NP acquisition. These IgG concentrations differ between serotypes. Ethnicity did not influence the association between high IgG concentrations and prevention of carriage despite differences in carriage rates. Since carriage determines transmission, these results may have important implications for herd protection.
  
  
  
  ClinicalTrials.gov number, NCT00508742; http://clinicaltrials.gov/ct2/show/NCT00508742.
authors.affiliation: The Faculty of Health Sciences, The Ben-Gurion University of the Negev, POB 653, Beer-Sheva 84105, Israel. Electronic address: rdagan@bgu.ac.il.
authors.forename: Ron
authors.initials: R
authors.lastname: Dagan
authors.affiliation: Pfizer Pharma GmbH, Linkstrasse 10, 10785 Berlin, Germany. Electronic address: Christine.Juergens@pfizer.com.
authors.forename: Christine
authors.initials: C
authors.lastname: Juergens
authors.affiliation: inVentiv Health Clinical, 504 Carnegie Center, Princeton, NJ 08540, USA. Electronic address: james.trammel@inventivhealth.com.
authors.forename: James
authors.initials: J
authors.lastname: Trammel
authors.affiliation: Pfizer Vaccines Research, Pfizer Inc., 401 N Middletown Road, Pearl River, NY 10965, USA. Electronic address: Scott.Patterson@Pfizer.com.
authors.forename: Scott
authors.initials: S
authors.lastname: Patterson
authors.affiliation: The Faculty of Health Sciences, The Ben-Gurion University of the Negev, POB 653, Beer-Sheva 84105, Israel; The Pediatric Infectious Disease Unit, Soroka University Medical Center, The Ben-Gurion University of the Negev, POB 151, Beer-Sheva 84101, Israel. Electronic address: dudi@bgu.ac.il.
authors.forename: David
authors.initials: D
authors.lastname: Greenberg
authors.affiliation: The Faculty of Health Sciences, The Ben-Gurion University of the Negev, POB 653, Beer-Sheva 84105, Israel; The Pediatric Infectious Disease Unit, Soroka University Medical Center, The Ben-Gurion University of the Negev, POB 151, Beer-Sheva 84101, Israel. Electronic address: givon@bgu.ac.il.
authors.forename: Noga
authors.initials: N
authors.lastname: Givon-Lavi
authors.affiliation: The Faculty of Health Sciences, The Ben-Gurion University of the Negev, POB 653, Beer-Sheva 84105, Israel; The Pediatric Infectious Disease Unit, Soroka University Medical Center, The Ben-Gurion University of the Negev, POB 151, Beer-Sheva 84101, Israel. Electronic address: npurat@bgu.ac.il.
authors.forename: Nurith
authors.initials: N
authors.lastname: Porat
authors.affiliation: Pfizer Vaccines Research, Pfizer Inc., 401 N Middletown Road, Pearl River, NY 10965, USA. Electronic address: Bill.Gruber@Pfizer.com.
authors.forename: William C
authors.initials: WC
authors.lastname: Gruber
authors.affiliation: Pfizer Vaccines Research, Pfizer Inc., 401 N Middletown Road, Pearl River, NY 10965, USA. Electronic address: Dan.Scott@Pfizer.com.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Scott
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood; D016667:Bacterial Capsules / Q000276:immunology*; D002353:Carrier State / Q000453:epidemiology / Q000276:immunology / Q000382:microbiology*; D005260:Female; D000069443:Heptavalent Pneumococcal Conjugate Vaccine / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D007557:Israel / Q000453:epidemiology; D008297:Male; D009305:Nasopharynx / Q000276:immunology / Q000382:microbiology*; D011008:Pneumococcal Infections / Q000453:epidemiology / Q000208:ethnology / Q000382:microbiology* / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D012044:Regression Analysis; D065288:Serogroup; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000302:isolation & purification*; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology
chemical_list: C538862:13-valent pneumococcal vaccine; D000907:Antibodies, Bacterial; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D007074:Immunoglobulin G; D022242:Pneumococcal Vaccines; D018074:Vaccines, Conjugate
keywords: Antibody concentrations; Indirect protection; Modeling; Nasopharyngeal colonization; Pneumococcal conjugate vaccine; Streptococcus pneumoniae