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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
Author: Mehring-Le Doare, Kirsty
ISNI:       0000 0004 5989 7123
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2016
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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.
Supervisor: Kampmann, Beate ; Gorringe, Andrew ; Heath, Paul Sponsor: Wellcome Trust ; Thrasher Foundation
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral