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Title: Maternal antibody interference, immunisation schedules, and protective antibody levels in infants
Author: Voysey, Merryn
ISNI:       0000 0004 7654 5162
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2018
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Vaccination programmes have been a cornerstone of public health policy globally for many decades. Infant immunisation programmes prevent millions of infections worldwide each year. In many cases infection is not just prevented in the immunised infants, but also in the wider population through the induction of herd effects. Whilst the efficacy and cost-effectiveness of infant immunisation programmes is well-established, the design of such programmes varies greatly from country to country. Within any single country, changes to the programme occur over time, when new vaccines are introduced, when the type or manufacturer of vaccines changes, or when there are changes to the number of doses, or the spacing of doses. In this thesis I explore the waning of maternal transplacental antibody, its effect on the immunogenicity of infant vaccines, and the timing and spacing of infant doses. I review the statistical methods for determining an antibody correlate of protection for vaccine-induced protection against disease and use new methods to derive serotype-specific correlates of protection for pneumococcal conjugate vaccines against the acquisition of carriage in infants. Using secondary analysis of serological data from 49 infant immunogenicity trials, I show that maternal antibody inhibits the immunogenicity of most infant vaccines. Higher antibody responses are observed in infants who commenced vaccination at an older age, independent of the interference caused by maternal vaccination. Current methods for determining antibody correlates of protection are not fit for purpose. Using generalised additive models of serological data I show that the antibody level associated with protection against pneumococcal carriage varies across serotypes, and is higher in low- and lower-middle income countries. These findings on key factors that influence the immune response in infants will help policy-makers in the UK and worldwide to make informed evidence-based decisions to protect the population against disease.
Supervisor: Pollard, Andrew J. ; Perera, Rafael ; Fanshawe, Thomas ; Sadarangani, Manish Sponsor: National Institute of Health Research
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available