Immunogenicity, Safety and Reactogenicity of a Booster Dose of the 10-Valent Pneumococcal Nontypeable H. influenzae Protein D Conjugate Vaccine Coadministered With DTPa-IPV-Hib in Dutch Children: A Randomized Controlled Trial.
BACKGROUND
Immune responses and safety profiles may be affected when vaccines are coadministered. We evaluated the immunogenicity, safety and reactogenicity of a booster dose of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D-conjugate (PHiD-CV; Synflorix GSK Vaccines) and DTPa-IPV-Hib (Pediacel Sanofi Pasteur MSD) when coadministered.


METHODS
We performed booster assessment in a randomized controlled trial in the Netherlands. Of 780 enrolled healthy infants, 774 toddlers participated in the booster phase and received (1:1:1) (1) PHiD-CV + DTPa-HBV-IPV/Hib (Infanrix hexa, GSK Vaccines), (2) PHiD-CV + DTPa-IPV-Hib, or (3) 7-valent pneumococcal conjugate vaccine (7vCRM, Prevenar/Prevnar, Pfizer, Inc.) + DTPa-IPV-Hib at 2, 3, 4 and 11-13 months old. Blood samples were taken postprimary, prebooster, 1 and 12 months postbooster.


RESULTS
Antipneumococcal antibody responses were comparable between both PHiD-CV groups, except for serotype 18C (conjugated to tetanus toxoid). Anti-18C antibody geometric mean concentrations (GMCs) were higher when coadministered with DTPa-HBV-IPV/Hib. For each vaccine serotype, the percentages of children with antibody concentration ≥ 0.20 μg/mL were within the same ranges between PHiD-CV groups (93.8%-100%). The same was observed for the percentages of participants with opsonophagocytic activity titer ≥ 8 (90.9%-100%). When comparing both DTPa-IPV-Hib groups, postbooster antidiphtheria antibody GMCs were higher when coadministered with 7vCRM, while antitetanus and antipolyribosyl-ribitol phosphate antibody GMCs were higher with PHiD-CV coadministration. Regardless, antibody levels to these antigens were well above thresholds. Safety and reactogenicity profiles were comparable between groups.


CONCLUSIONS
Coadministration of a booster dose of PHiD-CV and DTPa-IPV-Hib was immunogenic and well tolerated.
From the *Department of Pediatric Immunology and Infectious Diseases, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht, The Netherlands; †Research Center Linnaeus Institute, Spaarne Hospital, Hoofddorp, The Netherlands; ‡Vaccine Discovery and Development, and §XPE Pharma & Science for Vaccine Discovery and Development, GSK Vaccines, Wavre, Belgium.
Menno R
MR
van den Bergh
Judith
J
Spijkerman
Nancy
N
François
Kristien
K
Swinnen
Dorota
D
Borys
Lode
L
Schuerman
Reinier H
RH
Veenhoven
Elisabeth A M
EA
Sanders
D000907:Antibodies, Bacterial / Q000097:blood; D000914:Antibodies, Viral / Q000276:immunology; D002675:Child, Preschool; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D005260:Female; D018073:Haemophilus Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D017325:Hepatitis B Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary; D007072:Immunoglobulin D / Q000276:immunology*; D007223:Infant; D008297:Male; D011008:Pneumococcal Infections / Q000276:immunology / Q000517:prevention & control; D022242:Pneumococcal Vaccines / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D011054:Poliovirus Vaccine, Inactivated / Q000008:administration & dosage* / Q000009:adverse effects / Q000276:immunology; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
C538863:10-valent pneumococcal vaccine; D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; C513012:DTP-IPV-Hib vaccine; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; D017325:Hepatitis B Vaccines; D007072:Immunoglobulin D; C547294:PHiD-CV vaccine; D022242:Pneumococcal Vaccines; D011054:Poliovirus Vaccine, Inactivated; D017778:Vaccines, Combined; D018074:Vaccines, Conjugate; C541235:diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine; C541234:diphtheria-tetanus-five component acellular pertussis-inactivated poliomyelitis -Haemophilus influenzae type b conjugate vaccine