Speciation of the neisserial component of the infant upper respiratory tract microbiome by nonculture methods: impact of early life events and vaccination
File(s)
Author(s)
Fernandez Crespo, Roberto
Type
Thesis or dissertation
Abstract
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
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
Version
Open Access
Date Issued
2018-10
Date Awarded
2019-02
Copyright Statement
Creative Commons Attribution NonCommercial Licence
Advisor
Kroll, Simon
Langford, Paul
Sponsor
Meningitis Now
Grant Number
P54064
Publisher Department
Department of Medicine
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)