title: Correlates of protection of serotype-specific capsular antibody and invasive Group B Streptococcus disease in South African infants.
abstract: BACKGROUND
  Vaccinating pregnant women may prevent invasive Group B Streptococcus (GBS) disease in their young infants. In a low-middle income setting, we sought to determine an association between natural maternal antibody responses and the development of invasive GBS disease.
  
  
  METHODS
  We undertook a matched case-control study in Johannesburg, South Africa. Maternal and infant antibody concentrations were compared between serotype-specific Ia and III GBS cases and well-baby controls in which the mother was colonized with the same serotype.
  
  
  RESULTS
  The median maternal serotype Ia and III antibody concentrations (in μg/mL) were 0.05 (IQR: 0.02-0.24; n=27) and 0.14 (IQR: 0.08-0.33; n=29) in cases, and 0.29 (IQR: 0.06-1.60; n=43) and 0.29 (IQR: 0.13-0.58; n=31) in homotypic controls, respectively. A smaller proportion of cases as compared to homotypic controls had higher serotype Ia and III maternal antibody concentrations. Using Bayesian modeling, we demonstrated that the risk of invasive GBS disease was less than 10% with maternal antibody concentrations ≥ 6 μg/mL and ≥ 3 μg/mL for serotypes Ia and III, respectively.
  
  
  CONCLUSIONS
  Maternal capsular antibody concentrations are associated with the risk of invasive GBS disease in infants. In a low-middle income setting with a high burden of invasive disease, we have demonstrated a sero-correlate of protection for GBS serotypes Ia and III which could facilitate vaccine licensure.
authors.affiliation: Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, South Africa; Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, South Africa; Department of Paediatrics & Child Health, Faculty of Health Sciences, University of the Witwatersrand, South Africa.
authors.forename: Ziyaad
authors.initials: Z
authors.lastname: Dangor
authors.affiliation: Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, South Africa; Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, South Africa.
authors.forename: Gaurav
authors.initials: G
authors.lastname: Kwatra
authors.affiliation: Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, South Africa; Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, South Africa.
authors.forename: Alane
authors.initials: A
authors.lastname: Izu
authors.affiliation: Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, South Africa; Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, South Africa.
authors.forename: Peter
authors.initials: P
authors.lastname: Adrian
authors.affiliation: Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, South Africa; Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, South Africa.
authors.forename: Clare L
authors.initials: CL
authors.lastname: Cutland
authors.affiliation: Department of Paediatrics & Child Health, Faculty of Health Sciences, University of the Witwatersrand, South Africa.
authors.forename: Sithembiso
authors.initials: S
authors.lastname: Velaphi
authors.affiliation: Department of Paediatrics & Child Health, Faculty of Health Sciences, University of the Witwatersrand, South Africa.
authors.forename: Daynia
authors.initials: D
authors.lastname: Ballot
authors.affiliation: Department of Paediatrics & Child Health, Faculty of Health Sciences, University of the Witwatersrand, South Africa.
authors.forename: Gary
authors.initials: G
authors.lastname: Reubenson
authors.affiliation: Stat-Epi Associates Inc., FL, USA.
authors.forename: Elizabeth R
authors.initials: ER
authors.lastname: Zell
authors.affiliation: Department of Paediatrics & Child Health, Faculty of Health Sciences, University of the Witwatersrand, South Africa.
authors.forename: Sanjay G
authors.initials: SG
authors.lastname: Lala
authors.affiliation: Medical Research Council: Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, South Africa; Department of Science and Technology/National Research Foundation: Vaccine Preventable Diseases, University of the Witwatersrand, South Africa; National Institute for Communicable Diseases: A Division of National Health Laboratory Service, South Africa. Electronic address: madhis@rmpru.co.za.
authors.forename: Shabir A
authors.initials: SA
authors.lastname: Madhi
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood*; D016667:Bacterial Capsules / Q000276:immunology*; D015415:Biomarkers; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D011247:Pregnancy; D013019:South Africa; D013290:Streptococcal Infections / Q000276:immunology* / Q000517:prevention & control*; D013292:Streptococcus agalactiae / Q000276:immunology*; D055815:Young Adult
chemical_list: D000907:Antibodies, Bacterial; D015415:Biomarkers
keywords: Antibody; GBS; Group B Streptococcus; Immunity; Streptococcus agalactiae; Vaccine