Immunogenicity and Safety of a Combination Diphtheria, Tetanus Toxoid, Acellular Pertussis, Hepatitis B, and Inactivated Poliovirus Vaccine Coadministered with a 7-Valent Pneumococcal Conjugate Vaccine and a Haemophilus Influenzae Type b Conjugate Vaccine

  • Author Footnotes
    a Michael E. Pichichero, MD, has received research grants and/or honoraria from GlaxoSmithKline, Sanofi Pasteur Inc, Wyeth, and Merck & Co, Inc, for vaccine-related research.
    Michael E. Pichichero
    Correspondence
    Correspondence: Dr Michael E. Pichichero, University of Rochester Medical Center, 601 Elmwood Avenue, Box 672, Rochester, NY 14642.
    Footnotes
    a Michael E. Pichichero, MD, has received research grants and/or honoraria from GlaxoSmithKline, Sanofi Pasteur Inc, Wyeth, and Merck & Co, Inc, for vaccine-related research.
    Affiliations
    University of Rochester Medical Center, Rochester, New York
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  • Author Footnotes
    b Henry H. Bernstein, DO, has been a recipient of grant/research funding from GlaxoSmithKline.
    Henry Bernstein
    Footnotes
    b Henry H. Bernstein, DO, has been a recipient of grant/research funding from GlaxoSmithKline.
    Affiliations
    Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire
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  • Author Footnotes
    c Mark M. Blatter, MD, serves on the Speakers’ Bureaus for Sanofi Pasteur, Inc, and GlaxoSmithKline. He has received grant/research funding from GlaxoSmithKline, Sanofi Pasteur, Inc, Wyeth, Merck & Co, Inc, MedImmune, Inc, and Chiron Corporation.
    Mark M. Blatter
    Footnotes
    c Mark M. Blatter, MD, serves on the Speakers’ Bureaus for Sanofi Pasteur, Inc, and GlaxoSmithKline. He has received grant/research funding from GlaxoSmithKline, Sanofi Pasteur, Inc, Wyeth, Merck & Co, Inc, MedImmune, Inc, and Chiron Corporation.
    Affiliations
    Primary Physicians Research, Pittsburgh, Pennsylvania
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  • Author Footnotes
    d Lode Schuerman, MD, is an employee of GlaxoSmithKline and has stock options at the company.
    Lode Schuerman
    Footnotes
    d Lode Schuerman, MD, is an employee of GlaxoSmithKline and has stock options at the company.
    Affiliations
    University of Rochester Medical Center, Rochester, New York

    Dartmouth Medical School, Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire

    Primary Physicians Research, Pittsburgh, Pennsylvania

    GlaxoSmithKline Biologicals, Rixensart, Belgium

    formerly of Clinical/Medical Affairs, Vaccines-NA, GlaxoSmithKline, King of Prussia, Pennsylvania.
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  • Author Footnotes
    e Brigitte Cheuvart, PhD, is an employee of GlaxoSmithKline.
    Brigitte Cheuvart
    Footnotes
    e Brigitte Cheuvart, PhD, is an employee of GlaxoSmithKline.
    Affiliations
    GlaxoSmithKline Biologicals, Rixensart, Belgium
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  • Author Footnotes
    f Sandra J. Holmes, PhD, MHA, is a former employee of and previous consultant for GlaxoSmithKline.
    Sandra J. Holmes
    Footnotes
    f Sandra J. Holmes, PhD, MHA, is a former employee of and previous consultant for GlaxoSmithKline.
    Affiliations
    formerly of Clinical/Medical Affairs, Vaccines-NA, GlaxoSmithKline, King of Prussia, Pennsylvania.
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  • 085 Study Investigators
    Author Footnotes
    ⁎ Other members of the 085 Study Group are listed in the Appendix.
  • Author Footnotes
    ⁎ Other members of the 085 Study Group are listed in the Appendix.
    a Michael E. Pichichero, MD, has received research grants and/or honoraria from GlaxoSmithKline, Sanofi Pasteur Inc, Wyeth, and Merck & Co, Inc, for vaccine-related research.
    b Henry H. Bernstein, DO, has been a recipient of grant/research funding from GlaxoSmithKline.
    c Mark M. Blatter, MD, serves on the Speakers’ Bureaus for Sanofi Pasteur, Inc, and GlaxoSmithKline. He has received grant/research funding from GlaxoSmithKline, Sanofi Pasteur, Inc, Wyeth, Merck & Co, Inc, MedImmune, Inc, and Chiron Corporation.
    d Lode Schuerman, MD, is an employee of GlaxoSmithKline and has stock options at the company.
    e Brigitte Cheuvart, PhD, is an employee of GlaxoSmithKline.
    f Sandra J. Holmes, PhD, MHA, is a former employee of and previous consultant for GlaxoSmithKline.

      Objective

      To evaluate the immunogenicity and safety of a diphtheria and tetanus toxoids, acellular pertussis, hepatitis B, and inactivated poliovirus-containing vaccine (DTaP-HepB-IPV) coadministered with pneumococcal 7-valent conjugate vaccine (PCV-7) and Haemophilus influenzae type b vaccine (Hib), with separate vaccines concurrently, or staggered (delayed) administration of PCV-7.

      Study design

      At 2, 4, and 6 months of age, infants received either DTaP-HepB-IPV plus PCV-7 and Hib (n = 199), separate vaccines (n = 188), or DTaP-HepB-IPV plus Hib with PCV-7 administered 2 weeks later (n = 188). Blood was drawn before and after vaccination. Parents reported symptoms for 4 days after each dose and adverse events throughout the entire study.

      Results

      Immunogenicity in the Combination Vaccine Group was noninferior to that of the Separate and Staggered Vaccine Groups with respect to seroprotective rates for diphtheria, tetanus, and poliovirus and to geometric mean concentrations for pertussis. Seroprotective rates for HepB and Hib were not different between groups. Seropositivity for PCV-7 was high in all groups. Administration of combination vaccine appeared to be associated with higher rates of irritability, fever ≥100.4°F (38.0°C) and some local symptoms compared with separate vaccines (exploratory P < .05). No group differences were observed in rates of symptoms for which parents sought medical advice.

      Conclusions

      DTaP-HepB-IPV was highly immunogenic and well tolerated when coadministered with Hib and PCV-7 at 2, 4, and 6 months of age.

      Abbreviations:

      ANCOVA ( Analysis of covariance), CI ( Confidence interval), DT ( Diphtheria toxoid), DTaP ( Diphtheria–tetanus–acellular pertussis vaccine), ELISA ( Enzyme-linked immunosorbent assay), EL.U ( ELISA units), FHA ( Filamentous hemagglutinin), GMC ( Geometric mean concentration), GMT ( Geometric mean titer), HepB ( Hepatitis B vaccine), HBsAg ( Hepatitis B surface antigen), Hib ( Haemophilus influenzae type b vaccine), IPV ( Inactivated poliovirus vaccine), Lf ( Limit of flocculation unit), PCV-7 ( Pneumococcal 7-valent conjugate vaccine), PRN ( Pertactin), PRP ( Polyribosylribitol), PT ( Pertussis toxoid), TT ( Tetanus toxoid)
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