Transiently increased IgE responses in infants and pre-schoolers receiving only acellular Diphtheria-Pertussis-Tetanus (DTaP) vaccines compared to those initially receiving at least one dose of cellular vaccine (DTwP) - Immunological curiosity or canary in the mine?
Several previous studies have highlighted the strong Th2-polarising and IgE-promoting activity of the DTaP vaccine, but there is no evidence that this has pathological consequences and accordingly there is no current interest amongst vaccine developers in reformulating DTaP to attenuate these properties. In light of an apparent resurgence in pertussis in many countries, and emerging evidence from other areas of paediatric immunology of IgE-mediated interference with host defence mechanisms, this issue requires more detailed clarification.



We have re-evaluated the impact of DTaP-only versus mixed DTwP/DTaP vaccination on Th2-dependent "bystander" IgE responses in three cohorts of children under different priming conditions, encompassing both vaccine-targeted and unrelated antigens including food allergens.



We confirm the generalised IgE-trophic activity of the DTaP vaccine in pre-schoolers and demonstrate similar (albeit transient) effects in infants. We additionally demonstrate that use of an alternative mixed infant priming schedule encompassing an initial dose of DTwP significantly attenuates this property.



Central to our interpretation of these findings are studies demonstrating: (i) mixed DTwP/DTaP priming improves resistance to pertussis disease and attenuates the IgE-stimulatory component of long term vaccine-specific memory; (ii) IgE-mediated mechanisms can interfere with innate antiviral immunity and accordingly exacerbate airway symptoms in infected children. These observations, taken together with the data presented here, suggest a plausible mechanistic link between baseline pertussis-specific IgE titres in DTaP vaccinees and susceptibility to pertussis disease, which merits testing. Retrospective IgE analyses on sera collected from children at the time of presentation with pertussis could resolve this issue.
Telethon Kids Institute, The University of Western Australia, Perth, Australia. Electronic address: patrick.holt@telethonkids.org.au.
Patrick G
PG
Holt
Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, The University of Western Australia, Perth, Australia.
Tom
T
Snelling
Telethon Kids Institute, The University of Western Australia, Perth, Australia.
Olivia J
OJ
White
Queensland Children's Medical Research Institute, University of Queensland, Brisbane, Queensland, Australia.
Peter D
PD
Sly
Telethon Kids Institute, The University of Western Australia, Perth, Australia.
Nicholas
N
DeKlerk
Telethon Kids Institute, The University of Western Australia, Perth, Australia; Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, The University of Western Australia, Perth, Australia.
Jonathan
J
Carapetis
Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, The University of Western Australia, Perth, Australia.
Anita Van Den
AVD
Biggelaar
National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases, The Children's Hospital at Westmead, Sydney, Australia.
Nicholas
N
Wood
National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases, The Children's Hospital at Westmead, Sydney, Australia.
Peter
P
McIntyre
Discipline of Paediatrics, School of Medicine, University of Adelaide, Australia.
Michael
M
Gold
D000907:Antibodies, Bacterial / Q000097:blood*; D002675:Child, Preschool; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage / Q000627:therapeutic use*; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007073:Immunoglobulin E / Q000097:blood*; D007223:Infant; D012189:Retrospective Studies
D000907:Antibodies, Bacterial; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D022681:Diphtheria-Tetanus-acellular Pertussis Vaccines; D007073:Immunoglobulin E
Allergy; IgE; Infancy; Pertussis vaccine