Immunogenicity and safety of primary and booster vaccination with 2 investigational formulations of diphtheria, tetanus and Haemophilus influenzae type b antigens in a hexavalent DTPa-HBV-IPV/Hib combination vaccine in comparison with the licensed Infanrix hexa.
Safety and immunogenicity of 2 investigational formulations of diphtheria, tetanus and Haemophilus influenzae type b antigens of the combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliomyelitis-Hib vaccine (DTPa-HBV-IPV/Hib) were evaluated in a Primary (NCT01248884) and a Booster vaccination (NCT01453998) study. In the Primary study, 721 healthy infants (randomized 1:1:1) received 3 doses of DTPa-HBV-IPV/Hib formulation A (DATAPa-HBV-IPV/Hib), or B (DBTBPa-HBV-IPV/Hib) or the licensed DTPa-HBV-IPV/Hib vaccine (Infanrix hexa, GSK; control group) at 2, 3, 4 months of age. Infants were planned to receive a booster dose at 12-15 months of age with the same formulation received in the Primary study; however, following high incidence of fever associated with the investigational formulations in the Primary study, the Booster study protocol was amended and all infants yet to receive a booster dose (N = 385) received the licensed vaccine. In the Primary study, non-inferiority of 3-dose vaccination with investigational formulations compared with the licensed vaccine was not demonstrated due to anti-pertactin failing to meet the non-inferiority criterion. Post-primary vaccination, most infants had seroprotective levels of anti-diphtheria (100% of infants), anti-tetanus antigens (100%), against hepatitis B (≥ 97.5% across groups), polyribosyl-ribitol-phosphate (≥ 88.0%) and poliovirus types 1-3 (≥ 90.5%). Seropositivity rates for each pertussis antigen were 100% in all groups. Higher incidence of fever (> 38°C) was reported in infants receiving the investigational formulations (Primary study: 75.0% [A] and 72.1% [B] vs 58.8% [control]; Booster study, before amendment: 49.4% and 46.6% vs 37.4%, respectively). The development of the investigational formulations was not further pursued.
a Vaccine Research Center , University of Tampere , Tampere , Finland.
Timo
T
Vesikari
b Hospital Maternidad Nuestra Señora de la Altagracia Santo Domingo , Santo Domingo , Dominican Republic.
Luis
L
Rivera
c University of Tampere, Tampere Vaccine Research Clinic , Tampere , Finland.
Tiina
T
Korhonen
d Vaccine Research Center , University of Tampere, Järvenpää Vaccine Clinic , Järvenpää , Finland.
Anitta
A
Ahonen
e GSK , Wavre , Belgium.
Brigitte
B
Cheuvart
f Chiltern International c/o GSK , Wavre , Belgium.
Marjan
M
Hezareh
g GSK , Wavre , Belgium.
Winnie
W
Janssens
g GSK , Wavre , Belgium.
Narcisa
N
Mesaros
D000907:Antibodies, Bacterial / Q000097:blood*; D000914:Antibodies, Viral / Q000097:blood*; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D004311:Double-Blind Method; D064420:Drug-Related Side Effects and Adverse Reactions / Q000453:epidemiology* / Q000473:pathology; D005260:Female; D005334:Fever / Q000139:chemically induced* / Q000453:epidemiology; 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; D007115:Immunization Schedule; D007223:Infant; D008297:Male; D011054:Poliovirus Vaccine, Inactivated / Q000008:administration & dosage / Q000009:adverse effects* / Q000276:immunology*; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
D000907:Antibodies, Bacterial; D000914:Antibodies, Viral; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; D017325:Hepatitis B Vaccines; D011054:Poliovirus Vaccine, Inactivated; D017778:Vaccines, Combined; C541235:diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine
DTPa-HBV-IPV/Hib; Haemophilus influenzae type b; acellular pertussis; diphtheria; hepatitis B; immunogenicity; infants; poliovirus; safety; tetanus