title: Lot-to-lot Consistency, Safety, Tolerability and Immunogenicity of an Investigational Hexavalent Vaccine in US Infants.
abstract: This multicenter phase III study (NCT01340937) evaluated the consistency of immune responses to 3 separate lots of diphtheria-tetanus toxoids-acellular pertussis 5, inactivated poliovirus vaccine, Haemophilus influenzae type b, and hepatitis B (DTaP5-IPV-Hib-HepB), an investigational hexavalent vaccine (HV).
  
  
  
  Healthy infants were randomized (2:2:2:1) to receive HV or Pentacel (Control). Groups 1, 2 and 3 received HV at 2, 4 and 6 months, and Control at 15 months. Group 4 received Control at 2, 4, 6 and 15 months, plus Recombivax HB (HepB) at 2 and 6 months. Concomitant Prevnar 13 was given to all groups at 2, 4, 6 and 15 months; pentavalent rotavirus vaccine (RV5) was given to all groups at 2, 4 and 6 months. Blood specimens (3-5 mL) were collected immediately before administration of dose 1, postdose 3, immediately before toddler dose, and after toddler dose. Adverse events were recorded after each vaccination.
  
  
  
  The 3 manufacturing lots of HV induced consistent antibody responses to all antigens. Immunogenicity of HV was noninferior to Control for all antibodies, except for pertussis filamentous hemagglutinin geometric mean concentration postdose 3, and pertussis pertactin (PRN) geometric mean concentration after toddler dose. Postdose 3 immunogenicity of concomitantly administered Prevnar 13 was generally similar (except for serotype 6B) when given with HV or Control. Adverse events of HV were similar to Control, except for a higher rate of fever ≥38.0°C [49.2% vs. 35.4%, estimated difference 13.7% (8.4, 18.8)].
  
  
  
  HV demonstrated lot-to-lot manufacturing consistency; safety and immunogenicity were comparable with the licensed vaccines. HV provides a new combination vaccine option within the US 2-month, 4-month and 6-month vaccine series.
authors.affiliation: From the *Kentucky Pediatric/Adult Research, Inc., Bardstown, Kentucky; †Kaiser Permanente Vaccine Study Center, Oakland, California; ‡University of Texas Medical Branch, Galveston, Texas; §Midwest Children's Health Research Institute, Lincoln, Nevada; ¶University of North Texas Health Science Center, Fort Worth, Texas; ‖Merck & Co., Inc., Kenilworth, New Jersey; and **Sanofi Pasteur, Swiftwater, Pennsylvania.
authors.forename: Stanley L
authors.initials: SL
authors.lastname: Block
authors.forename: Nicola P
authors.initials: NP
authors.lastname: Klein
authors.forename: Kwabena
authors.initials: K
authors.lastname: Sarpong
authors.forename: Stephen
authors.initials: S
authors.lastname: Russell
authors.forename: John
authors.initials: J
authors.lastname: Fling
authors.forename: Maria
authors.initials: M
authors.lastname: Petrecz
authors.forename: Sheryl
authors.initials: S
authors.lastname: Flores
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.forename: Guanghan
authors.initials: G
authors.lastname: Liu
authors.forename: Jon E
authors.initials: JE
authors.lastname: Stek
authors.forename: Ginamarie
authors.initials: G
authors.lastname: Foglia
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Lee
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000009:adverse effects* / Q000276:immunology* / Q000592:standards*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology; D005260:Female; D005334:Fever / Q000453:epidemiology; D018073:Haemophilus Vaccines / Q000009:adverse effects* / Q000276:immunology* / Q000592:standards*; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D008297:Male; D011054:Poliovirus Vaccine, Inactivated / Q000009:adverse effects* / Q000276:immunology* / Q000592:standards*; D018074:Vaccines, Conjugate / Q000009:adverse effects / Q000276:immunology / Q000592:standards
chemical_list: D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; D011054:Poliovirus Vaccine, Inactivated; D018074:Vaccines, Conjugate; C541234:diphtheria-tetanus-five component acellular pertussis-inactivated poliomyelitis -Haemophilus influenzae type b conjugate vaccine