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Group-B Streptococci: developing a correlate of protection for future vaccine trials with the help of pregnant Gambian women and their infants

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Title: Group-B Streptococci: developing a correlate of protection for future vaccine trials with the help of pregnant Gambian women and their infants
Authors: Mehring-Le Doare, Kirsty
Item Type: Thesis or dissertation
Abstract: Background: Vertical GBS transmission is the prerequisite for early-onset disease. Disease protection is associated with maternally-derived anti-GBS antibody. This study investigates the correlation between serotype-specific functional antibody in cord sera and maternal/infant GBS colonisation, as a surrogate marker of GBS colonisation and thus disease protection. Methods: 750 Gambian mother/infant pairs were followed to day 60-89 postpartum. Maternal/infant GBS colonisation was determined by culture and polymerase chain reaction. Cord and infant serum were collected for functional antibody concentrations, analysed by flow cytometry. Results: Maternal colonisation was 33.7%; serotype (ST) V was most prevalent. Functional antibody concentration was lower in colonised- than in non-colonised mother/infant pairs at birth (STIa (p<0.001), STII (p<0.001), STIII (p<0.001) and STV (p<0.001)). Mother-colonised/infant-non-colonised pairs had significantly lower functional antibody concentration than non-colonised mother/infant pairs against STIa (p=0.001), STII (p=0.001), STIII (p<0.001) but not STV (p=1.0). Persistently colonised infants had lower functional antibody concentration than non-colonised infants against STII (p=0.04) and STV (p=0.01). Reduced infant colonisation risk was associated with functional antibody concentration above the 75th centile against STIa (p<0.001), STII (p<0.001), STIII (p=0.01) and STV (p<0.001). A ST-dependent threshold was observed above which infants were non-colonised at birth. Conclusions: Higher concentrations of functional maternally-derived antibodies are associated with a decreased risk of GBS colonisation in infants up to day 60-89 of life. Enhancing maternally-derived antibody concentrations through vaccination may reduce infant colonisation and so reduce the risk of GBS disease.
Content Version: Open Access
Issue Date: Feb-2016
Date Awarded: May-2016
URI: http://hdl.handle.net/10044/1/42363
DOI: https://doi.org/10.25560/42363
Supervisor: Kampmann, Beate
Gorringe, Andrew
Heath, Paul
Sponsor/Funder: Wellcome Trust (London, England)
Thrasher Foundation
Funder's Grant Number: WMNP_P52584
WMNP_P50865
Department: Department of Medicine
Publisher: Imperial College London
Qualification Level: Doctoral
Qualification Name: Doctor of Philosophy (PhD)
Appears in Collections:Medicine PhD theses



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