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Title: Speciation of the Neisserial component of the infant upper respiratory tract microbiome by nonculture methods : impact of early life events and vaccination
Author: Fernandez Crespo, Roberto
ISNI:       0000 0004 7658 994X
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2019
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Background: Neisseria meningitidis is a major causative agent of meningitis in infants. The introduction of conjugate vaccines has led to a decrease of incidence of disease caused by serogroups targeted by vaccines. Recently, a new vaccine, Bexsero®, was developed to target serogroup B isolates. Due to differences in composition with previous meningococcal vaccines, it was unclear if this vaccine could have an impact on N. meningitidis carriage, if it could impact the carriage of other Neisseria species, or other bacteria present in the upper respiratory tract. However, very little is known about what Neisseria species and in what proportion they appear in infants. Methods: Two sample cohorts were analysed. One was comprised of unvaccinated infants from which samples were collected at 6 weeks, 3, 4.5, 6, 9, 12, 18, 24 and 36 months of life. The second, was a group of samples from infants vaccinated with Bexsero® in two different vaccination schedules. Microbiome data was assessed by sequencing fragments of the 16S rRNA gene using the 454 GS FLX platform. Neisseria rplF gene fragments were sequenced using a novel approach using the MiSeq platform. Results and conclusions: Vaccination was associated with a change of 3% in the upper respiratory tract microbiome by the one-year time point. When considering Neisseria species data, less than 1% of the changes in abundance of Neisseria species populations were correlated with Bexsero® vaccination. Both of these results point towards Bexsero® not having a large impact on bacterial populations in the upper respiratory tract in infants. N. subflava and N. cinerea were the two most abundant species throughout the first three years of life and were accompanied by several other species in varying proportions. Multiple early life events, such as being exposed to cigarette smoke, were associated with changes in abundance of Neisseria species.
Supervisor: Kroll, Simon ; Langford, Paul Sponsor: Meningitis Now
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral