ORCID Profile
0000-0003-1113-1017
Current Organisations
University of Dublin Trinity College
,
University of Warwick
,
University of Oxford
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Publisher: American Society for Microbiology
Date: 15-07-2006
DOI: 10.1128/JVI.02014-05
Abstract: Human immunodeficiency virus type 1 (HIV-1) genetic ersity is a major obstacle for the design of a successful vaccine. Certain viral polymorphisms encode human leukocyte antigen (HLA)-associated immune escape, potentially overcoming limited vaccine protection. Although transmission of immune escape variants has been reported, the overall extent to which this phenomenon occurs in populations and the degree to which it contributes to HIV-1 viral evolution are unknown. Selection on the HIV-1 env gene at transmission favors neutralization-sensitive variants, but it is not known to what degree selection acts on the internal HIV-1 proteins to restrict or enhance the transmission of immune escape variants. Studies have suggested that HLA class I may determine susceptibility to HIV-1 infection, but a definitive role for HLA at transmission remains unproven. Comparing populations of acute seroconverters and chronically infected patients, we found no evidence of selection acting to restrict transmission of HIV-1 variants. We found that statistical associations previously reported in chronic infection between viral polymorphisms and HLA class I alleles are not present in acute infection, suggesting that the majority of viral polymorphisms in these patients are the result of transmission rather than de novo adaptation. Using four episodes of HIV-1 transmission in which the donors and recipients were both s led very close to the time of infection we found that, despite a transmission bottleneck, genetic variants of HIV-1 infection are transmitted in a frequency-dependent manner. As HIV-1 infections are seeded by unique donor-adapted viral variants, each episode is a highly in idual antigenic challenge. Host-specific, idiosyncratic HIV-1 antigenic ersity will seriously tax the efficacy of immunization based on consensus sequences.
Publisher: Oxford University Press (OUP)
Date: 10-2011
Publisher: Elsevier BV
Date: 04-2014
Publisher: Wiley
Date: 29-01-2013
DOI: 10.1111/MEC.12144
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 11-07-2008
Publisher: Oxford University Press (OUP)
Date: 15-04-2005
DOI: 10.1086/428590
Abstract: Neisseria meningitidis is a erse commensal bacterium that occasionally causes severe invasive disease. The relationship between meningococcal genotype and capsular polysaccharide, the principal virulence factor and vaccine component, was investigated in carried meningococci isolated from 8000 children and young adults in Bavaria, Germany. Of the 830 meningococci isolated (carriage rate, 10.4%) by microbiological techniques, 822 were characterized by serogrouping, multilocus sequence typing, and genetic analysis of the capsule region. Statistical and population genetic analyses were applied to these data. The rapid increase in carriage rates with age of carrier, the low prevalence of hyperinvasive meningococci, and the relative prevalence of the 4 disease-associated serogroups were consistent with earlier observations. There was no genetic structuring of the meningococcal population by age of carrier or s ling location however, there was significant geographic structuring of the meningococci isolated in civil, but not military, institutions. The rate of capsule gene expression did not vary with age of carrier or meningococcal genotype, except for serogroup C, for which increased expression was associated with ST-11 (formerly ET-37) complex meningococci. Serogroup C capsule expression during carriage may contribute to the invasive character of ST-11 complex meningococci and to the high efficacy of meningococcal serogroup C conjugate polysaccharide vaccine.
Publisher: Oxford University Press (OUP)
Date: 05-2008
DOI: 10.1086/586716
Abstract: A resurgence of Haemophilus influenzae type b (Hib) disease occurred in the United Kingdom between 1999 and 2003 and was partially attributed to lower immunogenicity of combination vaccines. The reservoir for Hib that led to transmission in this period is unknown. We estimated the point prevalence of Hib carriage in school-aged children and adults, using oropharyngeal swabbing and selective media. We characterized the Hib isolates by multilocus sequence typing (MLST) and measured Hib antibody concentrations in adults by enzyme-linked immunosorbent assay. Point prevalence for Hib carriage in 855 children aged 6-16 years was 4.2% (95% confidence interval [CI], 2.5%-5.9%). Five clonal groups of Hib were identified by MLST, 86% from the lineage of sequence type 6. No Hib was isolated in 385 adults (upper limit of 95% CI, 0.95%). The geometric mean concentration of serum antibody to polyribosylribitol phosphate was 0.47 microg/mL (95% CI, 0.37-0.59 mirog/mL) in adults. Hib carriage is common in school-aged children, who are a significant reservoir for ongoing transmission of Hib to susceptible in iduals in the United Kingdom. Surveillance of transmission and immunity across all ages of the population is essential to monitor the evolution of Hib epidemiology.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Noel McCarthy.