Imperial College London
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DrJohnLees

Faculty of Medicine, School of Public Health

Visiting Researcher
 
 
 
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Contact

 

+44 (0)20 7594 2939j.lees Website

 
 
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Location

 

UG4Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Kremer:2021:10.1101/2021.03.03.433546,
author = {Kremer, PHC and Ferwerda, B and Bootsma, HJ and Rots, NY and Wijmega-Monsuur, AJ and Sanders, EAM and Trzciski, K and Wyllie, AL and Turner, P and van, der Ende A and Brouwer, MC and Bentley, SD and van, de Beek D and Lees, JA},
doi = {10.1101/2021.03.03.433546},
title = {Pneumococcal genetic variability influences age-dependent bacterial carriage},
url = {http://dx.doi.org/10.1101/2021.03.03.433546},
year = {2021}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - <jats:title>Abstract</jats:title><jats:p>The pneumococcal conjugate vaccine (PCV) primarily reduces disease burden in adults through a reduction in carriage prevalence of invasive serotypes in children. Current vaccine formulations are the same for both adults and children, but tailoring these formulations to age category could optimize vaccine efficacy. Identification of specific pneumococcal genetic factors associated with carriage in younger or older age groups may suggest alternative formulations and contribute to a better mechanistic understanding of immunity. Here, we used whole genome sequencing to dissect pneumococcal variation associated with age. We performed genome sequencing in a large carriage cohort, and conducted a meta-analysis with an existing carriage study. We compiled a dictionary of pathogen genetic variation including serotype, sequence cluster, sequence elements, SNPs, burden combined rare variants, and clusters of orthologous genes (COGs) for each cohort – all of which used in a genome-wide association with host age. Age-dependent colonization had some heritability, though this varied between cohorts (h<jats:sup>2</jats:sup> = 0.10, 0.00 – 0.69 95% CI in the first; h<jats:sup>2</jats:sup> = 0.46, 0.33 – 0.60 95% CI in the second cohort). We found that serotypes and genetic background (strain) explained most of the heritability in each cohort (h<jats:sup>2</jats:sup><jats:sub>serotype</jats:sub> = 0.06 and h<jats:sup>2</jats:sup><jats:sub>GPSC</jats:sub> = 0.04 in the first; h<jats:sup>2</jats:sup><jats:sub>serotype</jats:sub> = 0.20 and h<jats:sup>2</jats:sup><jats:sub>GPSC</jats:sub> = 0.23 in the second cohort). We found one candidate association (p = 1.2×10<jats:sup>−9</jats:sup>) upstream of an accessory Sec-dependent serine-rich glycoprotein adhesin. Overall, a
AU  - Kremer,PHC
AU  - Ferwerda,B
AU  - Bootsma,HJ
AU  - Rots,NY
AU  - Wijmega-Monsuur,AJ
AU  - Sanders,EAM
AU  - Trzciski,K
AU  - Wyllie,AL
AU  - Turner,P
AU  - van,der Ende A
AU  - Brouwer,MC
AU  - Bentley,SD
AU  - van,de Beek D
AU  - Lees,JA
DO  - 10.1101/2021.03.03.433546
PY  - 2021///
TI  - Pneumococcal genetic variability influences age-dependent bacterial carriage
UR  - http://dx.doi.org/10.1101/2021.03.03.433546
ER  -
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