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 |
Externí odkaz: |