Bacille Calmette-Guérin (BCG) vaccination at birth and antibody responses to childhood vaccines. A randomised clinical trial.
BCG vaccination has been associated with beneficial non-specific effects on child health. Some immunological studies have reported heterologous effects of vaccines on antibody responses to heterologous vaccines. Within a randomised clinical trial of Bacille Calmette-Guérin (BCG) vaccination at birth, The Danish Calmette Study, we investigated the effect of BCG at birth on the antibody response to the three routine vaccines against DiTeKiPol/Act-Hib and Prevenar 13 in a subgroup of participants.



Within 7days after birth, children were randomised 1:1 to BCG vaccination or to the control group (no intervention). After three routine vaccinations given at age 3, 5 and 12months, antibodies against DiTeKiPol/Act-Hib and Prevenar 13 (Streptococcus pneumoniae serotype type 4, 6B, 9V, 14, 18C, 19F and 23F) were measured 4weeks after the third vaccine dose.



Among the 300 included children (178 BCG; 122 controls), almost all children (>96%) had antibody responses above the protective levels. Overall BCG vaccination at birth did not affect the antibody level. When stratifying by 'age at randomisation' we found a possible inducing effect of BCG on antibodies against B. pertussis and all pneumococcal serotypes, when BCG was given after the first day of life. Girls had significantly higher antibody levels for Haemophilus influenza type b and pneumococcus than boys.



Three routine vaccinations with DiTeKiPol/Act-Hib and Prevenar 13 induced sero-protective levels in almost all children. No overall effect of neonatal BCG vaccination was observed.
Department of Pediatrics, 460, Copenhagen University Hospital, Hvidovre, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark. Electronic address: thomas.nissen@dadlnet.dk.
Thomas Nørrelykke
TN
Nissen
Department of Pediatrics, 460, Copenhagen University Hospital, Hvidovre, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark. Electronic address: ninabirk@dadlnet.dk.
Nina Marie
NM
Birk
National Institute for Public health and the Environment, Centre for Infectious Disease Control, Antonie van Leeuwenhoeklaan 9, 3721 MA Bilthoven, The Netherlands. Electronic address: gaby.smits@rivm.nl.
Gaby
G
Smits
Department of Pediatrics, 460, Copenhagen University Hospital, Hvidovre, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark. Electronic address: Dorthe.Lisbeth.Jeppesen@regionh.dk.
Dorthe Lisbeth
DL
Jeppesen
The Child and Adolescent Clinic 4072, Juliane Marie Centret, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, DK-2100 Copenhagen Ø, Denmark. Electronic address: Lone.graff.stensballe@regionh.dk.
Lone Graff
LG
Stensballe
Division of Experimental Internal Medicine, Department of Internal Medicine, Radboud University Medical Center, Geert Grooteplein 10, 6525GA Nijmegen, The Netherlands. Electronic address: Mihai.Netea@radboudumc.nl.
Mihai G
MG
Netea
National Institute for Public health and the Environment, Centre for Infectious Disease Control, Antonie van Leeuwenhoeklaan 9, 3721 MA Bilthoven, The Netherlands. Electronic address: fiona.van.der.klis@rivm.nl.
Fiona
F
van der Klis
Research Center for Vitamins and Vaccines (CVIVA), Bandim Health Project, Statens Serum Institut, Artillerivej 5, DK-2300 Copenhagen S, Denmark; Odense Patient data Explorative Network, Odense University Hospital/Institute of Clinical Research, University of Southern Denmark, Odense, Denmark. Electronic address: cb@ssi.dk.
Christine Stabell
CS
Benn
Department of Pediatrics, 460, Copenhagen University Hospital, Hvidovre, Kettegaard Allé 30, DK-2650 Hvidovre, Denmark. Electronic address: pryds@dadlnet.dk.
Ole
O
Pryds
D000276:Adjuvants, Immunologic / Q000008:administration & dosage; D000907:Antibodies, Bacterial / Q000097:blood*; D000917:Antibody Formation; D001500:BCG Vaccine / Q000008:administration & dosage / Q000276:immunology*; D003718:Denmark; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage / Q000276:immunology*; D005260:Female; D018073:Haemophilus Vaccines / Q000008:administration & dosage / Q000276:immunology*; D000069443:Heptavalent Pneumococcal Conjugate Vaccine / Q000008:administration & dosage / Q000276:immunology*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011054:Poliovirus Vaccine, Inactivated / Q000008:administration & dosage / Q000276:immunology*; D011247:Pregnancy; D017778:Vaccines, Combined / Q000008:administration & dosage / Q000276:immunology
C570267:Act-Hib vaccine; D000276:Adjuvants, Immunologic; D000907:Antibodies, Bacterial; D001500:BCG Vaccine; C513012:DTP-IPV-Hib vaccine; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; D000069443:Heptavalent Pneumococcal Conjugate Vaccine; D011054:Poliovirus Vaccine, Inactivated; D017778:Vaccines, Combined
BCG; Children; Clinical trial; Heterologous immunity; Non-specific effects; Vaccine antibodies