Genetic stability of pneumococcal isolates during 35 days of human experimental carriage

Autor: Jenna F. Gritzfeld, P. Coupland, Stephen D. Bentley, Rebecca A. Gladstone, Stephen B. Gordon
Rok vydání: 2014
Předmět:
Pneumococcal carriage
Adult
DNA
Bacterial
wc_20
Pneumococcal disease
Experimental human pneumococcal carriage
Adolescent
Genotype
Genetic stability
medicine.disease_cause
qw_806
Polymorphism
Single Nucleotide
qw_805
Pneumococcal Infections
Article
03 medical and health sciences
Young Adult
0302 clinical medicine
Immunology and Microbiology(all)
Streptococcus pneumoniae
Vaccine efficacy against carriage (VEcol)
Medicine
Humans
030212 general & internal medicine
030304 developmental biology
0303 health sciences
General Veterinary
General Immunology and Microbiology
Transmission (medicine)
business.industry
Public Health
Environmental and Occupational Health
Genetic Variation
wc_217
Sequence Analysis
DNA
Pneumococcal vaccines
Middle Aged
medicine.disease
Vaccine efficacy
veterinary(all)
Healthy Volunteers
3. Good health
Pneumococcal infections
Carriage
Infectious Diseases
Immunology
Carrier State
Molecular Medicine
business
Zdroj: Vaccine
ISSN: 1873-2518
0264-410X
Popis: Highlights • The experimental human carriage (EHPC) inoculum is genetically stable over 35 days. • Documentation of stability further addresses concerns of validity and safety of EHPC. • Confidence in EHPC to safely and reproducibly measure VEcol is key to aiding vaccine licensure.
Background Pneumococcal carriage is a reservoir for transmission and a precursor to pneumococcal disease. The experimental human pneumococcal carriage model provides a useful tool to aid vaccine licensure through the measurement of vaccine efficacy against carriage (VEcol). Documentation of the genetic stability of the experimental human pneumococcal carriage model is important to further strengthen confidence in its safety and conclusions, enabling it to further facilitate vaccine licensure through providing evidence of VEcol. Methods 229 isolates were sequenced from 10 volunteers in whom experimental human pneumococcal carriage was established, sampled over a period of 35 days. Multiple isolates from within a single volunteer at a single time provided a deep resolution for detecting variation. HiSeq data from the isolates were mapped against a PacBio reference of the inoculum to call variable sites. Results The observed variation between experimental carriage isolates was minimal with the maximum SNP distance between any isolate and the reference being 3 SNPs. Conclusion The low-level variation described provides evidence for the stability of the experimental human pneumococcal carriage model over 35 days, which can be reliably and confidently used to measure VEcol and aid future progression of pneumococcal vaccination.
Databáze: OpenAIRE
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