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Title: Maternal and infant immune responses to pertussis vaccination in pregnancy
Author: Rice, Thomas Francis
ISNI:       0000 0004 9351 0201
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2019
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Background: In the United Kingdom in 2012, there was a pertussis epidemic that disproportionately affected infants too young to be protected by immunisation. In an attempt to protect this vulnerable age group, pertussis vaccination was introduced for pregnant women. However, how immune responses in mothers and infants are altered following pertussis vaccination during pregnancy requires further investigation. Methods: Women were recruited from tetanus-diphtheria-acellular pertussis (Tdap)-vaccinated and unvaccinated pregnancies. Blood was obtained from women during pregnancy and at birth, from the cord of the placenta, and from infants at seven weeks (pre-primary pertussis immunisation) and five months of age (post-primary pertussis immunisation). Investigations measured antibody responses to Tdap vaccination and the primary series of paediatric vaccines, innate cytokine responses to Bordetella pertussis and strains lacking Tdap vaccine antigens, the phenotype of innate cells present in infants at birth and heterologous effects of Tdap vaccination during pregnancy in mothers and infants. Results: Tdap vaccination significantly boosted antibody to all Tdap antigens in women at birth and infants up to seven weeks of age. At five months of age, infants from Tdap-vaccinated and unvaccinated pregnancies had comparable levels of antibody to all Tdap vaccine antigens. Tdap vaccination during pregnancy boosted innate cytokine responses to B. pertussis in mothers, but had less of an effect in infants. Innate cytokine responses to B. pertussis were strain-dependent, with strains lacking antigens contained in the Tdap vaccine inducing greater cytokine production. Tdap vaccination during pregnancy impacted the frequency of monocyte subsets in infants at birth, as well as dampening cytokine expression. Tdap vaccination induced heterologous effects in mothers and infants, with reduced cytokine responses to bacterial and viral ligands. Conclusions: Tdap vaccination during pregnancy influences both innate and adaptive immunity in mothers and infants. Longitudinal studies of large cohorts of mother-infant pairs are required to determine the clinical implications of these findings.
Supervisor: Holder, Beth ; Kampmann, Beate Sponsor: National Institute for Health Research ; Imperial College London
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral