Holt PGa, Snelling Tb, White OJa, Sly PDc, deKlerk Na, Carapetis Ja,b, Van Den Biggelaar Ab, Wood Nd, McIntyre Pd, Gold Me
a The Kids Research Institute Australia, The University of Western Australia, Perth, Australia
b Wesfarmers Centre of Vaccines and Infectious Diseases, The Kids Research Institute Australia, The University of Western Australia, Perth, Australia
c Queensland Children’s Medical Research Institute, University of Queensland, Brisbane, Queensland
d National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases, The Children’s Hospital at Westmead, Sydney, Australia
e Discipline of Paediatrics, School of Medicine, University of Adelaide, Australia
In the late 1990s the original version of the DTP vaccine which contained bacterial cell walls (DTwP) was replaced by a better chemically defined (“cleaner”) formulation which lacked the cell wall components (acellular DTaP). Despite the effectiveness of DTaP in preventing severe Pertussis infection (“whooping cough”) which requires hospitalization, overall rates of Pertussis infections in the community are now rising, suggesting that there is a need to improve the vaccine. This project tested the degree to which the vaccine promotes “bystander” IgE responses to vaccine antigens which theoretically may interfere with vaccine performance, and whether these bystander responses also affect responses to food allergens. To do this 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, using stored serum samples collected during immunization. We confirmed the generalised IgE-stimulatory activity of the DTaP vaccine on responses to vaccine-specific antigens in pre-schoolers, and demonstrated similar effects in infants on food allergen-specific IgE which were mild/transient and unlikely to be clinically significant. We additionally showed that use of an alternative mixed infant priming schedule encompassing an initial dose of DTwP significantly attenuates this IgE-stimulatory property. These findings are being followed up via a RCT led by Dr T Snelling, comparing DTwP DTaP versus pure DTaP vaccination, which is planned for 2017.
Plain language summary: Community rates of whooping cough are increasing world wide, suggesting that the current vaccine is not 100% effective. We are seeking more detailed information on how the immune system of infants responds to the vaccine, with the aim of identifying which aspects of the immune response need to be improved to optimize protection. This information will be made available to vaccine developers and health regulatory authorities, to inform debate surrounding future development of an improved vaccine.
Funder: Internal funding from The Kids Research Institute Australia.