Characterisation of immune responses to varicella vaccination in relation to clinical outcome

This thesis examines both humoral and cellular adaptive immune responses to varicella vaccination (up to 18 months post immunisation), in an ethnically diverse population of healthcare workers. Using two parameters of humoral immunity at six weeks post first vaccination; (avidity readings 60%, and a TRFIA reading 400mIU/mL) a cut-off of 130mIU/mL was defined for a more sensitive in house immuno assay (TRFIA), in this vaccinated adult population. Using these cut-offs, three patterns of antibody responses were identified; primary responders who seroconverted following vaccination, secondary responders who had pre-existing immunity and subjects who responded poorly to vaccination. Demographic and immunological characteristics of each subset were examined. An association between black ethnicity and lower antibody titre to vaccination in primary responders was identified, whilst Caucasians were more likely to have a history and pre-existing immunity, in keeping with the epidemiology of chickenpox in temperate climates. The follow-up study revealed that affinity maturation to VZV can take longer than 18 months in response to vaccination. At follow-up, 25% of subjects recruited at this time point were seronegative by TRFIA. Seroconversion after two doses of vaccine and a TRFIA titre of