Patrick G Holt1, Tom Snelling2, Olivia J White3, Peter D Sly4, Nicholas DeKlerk3, Jonathan Carapetis5, Anita Van Den Biggelaar2, Nicholas Wood6, Peter McIntyre6, Michael Gold7. 1. Telethon Kids Institute, The University of Western Australia, Perth, Australia. Electronic address: patrick.holt@telethonkids.org.au. 2. Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, The University of Western Australia, Perth, Australia. 3. Telethon Kids Institute, The University of Western Australia, Perth, Australia. 4. Queensland Children's Medical Research Institute, University of Queensland, Brisbane, Queensland, Australia. 5. 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. 6. National Centre for Immunisation Research and Surveillance of Vaccine Preventable Diseases, The Children's Hospital at Westmead, Sydney, Australia. 7. Discipline of Paediatrics, School of Medicine, University of Adelaide, Australia.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. INTERPRETATION: 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.
BACKGROUND: 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. METHODS: 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. RESULTS: 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. INTERPRETATION: 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.
Authors: Gladymar Perez Chacon; Jessica Ramsay; Christopher G Brennan-Jones; Marie J Estcourt; Peter Richmond; Patrick Holt; Tom Snelling Journal: Cochrane Database Syst Rev Date: 2021-09-06
Authors: Ricardo da Silva Antunes; Ferran Soldevila; Mikhail Pomaznoy; Mariana Babor; Jason Bennett; Yuan Tian; Natalie Khalil; Yu Qian; Aishwarya Mandava; Richard H Scheuermann; Mario Cortese; Bali Pulendran; Christopher D Petro; Adrienne P Gilkes; Lisa A Purcell; Alessandro Sette; Bjoern Peters Journal: JCI Insight Date: 2021-04-08
Authors: Marie J Estcourt; Julie A Marsh; Dianne E Campbell; Michael S Gold; Katrina J Allen; Peter Richmond; Claire S Waddington; Thomas L Snelling Journal: BMJ Open Date: 2018-01-31 Impact factor: 2.692
Authors: Gladymar Perez Chacon; Marie J Estcourt; James Totterdell; Dianne E Campbell; Kirsten P Perrett; Julie A Marsh; Peter C Richmond; Nicholas Wood; Michael S Gold; Patrick G Holt; Claire S Waddington; Thomas L Snelling Journal: BMJ Open Date: 2020-12-17 Impact factor: 3.006