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Title: Persistence of protection against invasive bacteria : memory B cell responses in infants after immunisation
Author: Blanchard Rohner, Géraldine
ISNI:       0000 0004 2676 309X
Awarding Body: University of Oxford
Current Institution: University of Oxford
Date of Award: 2008
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Rapid waning of antibody and vaccine effectiveness is observed following infant immunisation with protein-polysaccharide conjugate vaccines. This is despite the demonstrable presence of immunological memory. However, disease can develop within a few days of carriage acquisition of encapsulated bacteria. Persistence of functional antibody, therefore, appears to be the key determinant of long-term protection against invasive bacterial diseases. Antibody persistence is thought to depend on the survival of long-lived plasma cells and memory B cells generated in germinal centres (GC). Using the ELISpot method, the kinetics of the B cell response following a booster dose of MenC conjugate vaccine (MenCV) at one year of age, and following a 2 dose-primary course of a new tetravalent meningococcal vaccine (MenACWY-CRM197) given at 2 and 4 months of age, were determined. It was found that priming with these vaccines induced protective antibody levels in the majority of children but detectable memory B cells only in a subset of children. A strong association was found between the level of polysaccharide-specific antibody and memory B cells produced after priming, and the persistence of functional antibody at one year of age. The kinetics of a primary B cell response were determined in healthy adults after immunisation with rabies vaccine, and compared to the B cell response following primary immunisation with MenCV in 2 months old infants. The timing of appearance of the B cells in peripheral blood was similar in infants and adults, although the magnitude of the response was slightly lower in infants. These observations suggest that long-term humoral immunity induced by immunisation with protein-polysaccharide conjugate vaccines in early infancy depends on the production of adequate GCs during priming. The children who generate efficient GCs during priming (identified by higher production of memory B cells, plasma cells and Abs) may best maintain protective antibody levels in the long-term, while those children generating less efficient GCs, have a smaller B cell pool, lower antibody response during priming, and might not maintain protective antibody levels in the long-term.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available