title: Antibody responses after primary immunization in infants born to women receiving a pertussis-containing vaccine during pregnancy: single arm observational study with a historical comparator.
abstract: BACKGROUND
  In England, antenatal pertussis immunization using a tetanus/low-dose diphtheria/5-component acellular-pertussis/inactivated-polio (TdaP5/IPV) vaccine was introduced in October 2012. We assessed infant responses to antigens in the maternal vaccine and to those conjugated to tetanus (TT) or the diphtheria toxin variant, CRM.
  
  
  METHODS
  Infants of 141 TdaP5/IPV-vaccinated mothers in Southern England immunized with DTaP5/IPV/Haemophilus influenzae b (Hib-TT) vaccine at 2-3-4 months, 13-valent pneumococcal vaccine (PCV13, CRM-conjugated) at 2-4 months and 1 or 2 meningococcal C vaccine (MCC-CRM- or MCC-TT) doses at 3-4 months had blood samples taken at 2 and/or 5 months of age.
  
  
  RESULTS
  Antibody responses to pertussis toxin (PT), filamentous hemagglutinin (FHA), fimbriae 2 + 3 (FIMs), diphtheria, tetanus, Hib, MCC and PCV13 serotypes were compared to responses in a historical cohort of 246 infants born to mothers not vaccinated in pregnancy. Infants had high pertussis antibody concentrations pre-immunization but only PT antibodies increased post-immunization (fold-change, 2.64; 95% confidence interval [CI], 2.12-3.30; P < .001), whereas FHA antibodies fell (fold-change, 0.56; 95% CI, .48-.65; P < .001). Compared with infants of unvaccinated mothers, PT, FHA, and FIMs antibodies were lower post-vaccination, with fold-differences of 0.67 (0.58-0.77; P < .001), 0.62 (0.54-0.71; P < .001) and 0.51 (0.42-0.62; P < .001), respectively. Antibodies to diphtheria and some CRM-conjugated antigens were also lower, although most infants achieved protective thresholds; antibodies to tetanus and Hib were higher.
  
  
  CONCLUSIONS
  Antenatal pertussis immunization results in high infant pre-immunization antibody concentrations, but blunts subsequent responses to pertussis vaccine and some CRM-conjugated antigens. In countries with no pertussis booster until school age, continued monitoring of protection against pertussis is essential.
authors.affiliation: Immunisation, Hepatitis and Blood Safety Department, Public Health England Paediatric Infectious Diseases Research Group, Institute for Infection and Immunity, St. George's, University of London.
authors.forename: Shamez N
authors.initials: SN
authors.lastname: Ladhani
authors.affiliation: Statistics, Modelling and Economics and Immunisation, Public Health England, London.
authors.forename: Nick J
authors.initials: NJ
authors.lastname: Andrews
authors.affiliation: Immunisation, Hepatitis and Blood Safety Department, Public Health England.
authors.forename: Jo
authors.initials: J
authors.lastname: Southern
authors.affiliation: Paediatric Infectious Diseases Research Group, Institute for Infection and Immunity, St. George's, University of London.
authors.forename: Christine E
authors.initials: CE
authors.lastname: Jones
authors.affiliation: Immunisation, Hepatitis and Blood Safety Department, Public Health England.
authors.forename: Gayatri
authors.initials: G
authors.lastname: Amirthalingam
authors.affiliation: Immunisation, Hepatitis and Blood Safety Department, Public Health England.
authors.forename: Pauline A
authors.initials: PA
authors.lastname: Waight
authors.affiliation: Immunoassay Laboratory, Public Health England, Porton Down.
authors.forename: Anna
authors.initials: A
authors.lastname: England
authors.affiliation: Immunoassay Laboratory, Public Health England, Porton Down.
authors.forename: Mary
authors.initials: M
authors.lastname: Matheson
authors.affiliation: Vaccine Evaluation Unit, Public Health England, Manchester Royal Infirmary.
authors.forename: Xilian
authors.initials: X
authors.lastname: Bai
authors.affiliation: Vaccine Evaluation Unit, Public Health England, Manchester Royal Infirmary.
authors.forename: Helen
authors.initials: H
authors.lastname: Findlow
authors.affiliation: Immunobiology Unit, Institute of Child Health, University College, London, United Kingdom.
authors.forename: Polly
authors.initials: P
authors.lastname: Burbidge
authors.affiliation: Immunobiology Unit, Institute of Child Health, University College, London, United Kingdom.
authors.forename: Vasili
authors.initials: V
authors.lastname: Thalasselis
authors.affiliation: Immunoassay Laboratory, Public Health England, Porton Down.
authors.forename: Bassam
authors.initials: B
authors.lastname: Hallis
authors.affiliation: Immunobiology Unit, Institute of Child Health, University College, London, United Kingdom.
authors.forename: David
authors.initials: D
authors.lastname: Goldblatt
authors.affiliation: Vaccine Evaluation Unit, Public Health England, Manchester Royal Infirmary.
authors.forename: Ray
authors.initials: R
authors.lastname: Borrow
authors.affiliation: Paediatric Infectious Diseases Research Group, Institute for Infection and Immunity, St. George's, University of London.
authors.forename: Paul T
authors.initials: PT
authors.lastname: Heath
authors.affiliation: Immunisation, Hepatitis and Blood Safety Department, Public Health England.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Miller
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood*; D000942:Antigens, Bacterial / Q000276:immunology; D001886:Bordetella pertussis / Q000276:immunology*; D015331:Cohort Studies; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines / Q000008:administration & dosage / Q000276:immunology*; D004739:England; D005260:Female; D018073:Haemophilus Vaccines / Q000008:administration & dosage / Q000276:immunology; D006801:Humans; D007112:Immunity, Maternally-Acquired; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D008297:Male; D022401:Meningococcal Vaccines / Q000008:administration & dosage; D022242:Pneumococcal Vaccines / Q000008:administration & dosage / Q000276:immunology; D011054:Poliovirus Vaccine, Inactivated / Q000008:administration & dosage; D011247:Pregnancy; D013745:Tetanus Toxoid / Q000008:administration & dosage / Q000276:immunology; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology; D014917:Whooping Cough / Q000276:immunology* / Q000517:prevention & control
chemical_list: C538862:13-valent pneumococcal vaccine; D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines; D018073:Haemophilus Vaccines; C055753:Haemophilus influenza type b polysaccharide vaccine-tetanus toxin conjugate; D007074:Immunoglobulin G; D022401:Meningococcal Vaccines; D022242:Pneumococcal Vaccines; D011054:Poliovirus Vaccine, Inactivated; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate
keywords: antenatal immunization; conjugate vaccines; immune interference; maternal vaccination; pertussis