Dataset Information

Modulation of nasopharyngeal innate defenses by viral coinfection predisposes individuals to experimental pneumococcal carriage.

ABSTRACT: Increased nasopharyngeal colonization density has been associated with pneumonia. We used experimental human pneumococcal carriage to investigate whether upper respiratory tract viral infection predisposes individuals to carriage. A total of 101 healthy subjects were screened for respiratory virus before pneumococcal intranasal challenge. Virus was associated with increased odds of colonization (75% virus positive became colonized vs. 46% virus-negative subjects; P=0.02). Nasal Factor H (FH) levels were increased in virus-positive subjects and were associated with increased colonization density. Using an in vitro epithelial model we explored the impact of increased mucosal FH in the context of coinfection. Epithelial inflammation and FH binding resulted in increased pneumococcal adherence to the epithelium. Binding was partially blocked by antibodies targeting the FH-binding protein Pneumococcal surface protein C (PspC). PspC epitope mapping revealed individuals lacked antibodies against the FH binding region. We propose that FH binding to PspC in vivo masks this binding site, enabling FH to facilitate pneumococcal/epithelial attachment during viral infection despite the presence of anti-PspC antibodies. We propose that a PspC-based vaccine lacking binding to FH could reduce pneumococcal colonization, and may have enhanced protection in those with underlying viral infection.

SUBMITTER: Glennie S

PROVIDER: S-EPMC4703943 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Modulation of nasopharyngeal innate defenses by viral coinfection predisposes individuals to experimental pneumococcal carriage.

Glennie S S Gritzfeld J F JF Pennington S H SH Garner-Jones M M Coombes N N Hopkins M J MJ Vadesilho C F CF Miyaji E N EN Wang D D Wright A D AD Collins A M AM Gordon S B SB Ferreira D M DM

Mucosal immunology 20150429 1

Increased nasopharyngeal colonization density has been associated with pneumonia. We used experimental human pneumococcal carriage to investigate whether upper respiratory tract viral infection predisposes individuals to carriage. A total of 101 healthy subjects were screened for respiratory virus before pneumococcal intranasal challenge. Virus was associated with increased odds of colonization (75% virus positive became colonized vs. 46% virus-negative subjects; P=0.02). Nasal Factor H (FH) lev ...[more]

PMID: 25921341

Similar Datasets

Project description:Pneumococcal disease is a major contributor to global childhood morbidity and mortality and is more common in low- and middle-income countries (LMICs) than in high-income countries. Pneumococcal carriage is a prerequisite for pneumococcal disease. Pneumococcal conjugate vaccine reduces vaccine-type carriage and disease. However, pneumococcal carriage and disease persist, and it is important to identify other potentially modifiable factors associated with pneumococcal carriage and determine if risk factors differ between low, middle, and high-income countries. This information may help inform pneumococcal disease prevention programs. This systematic literature review describes factors associated with pneumococcal carriage stratified by country income status and summarises pneumococcal carriage rates for included studies. We undertook a systematic search of English-language pneumococcal nasopharyngeal carriage studies up to 30th June 2021. Peer-reviewed studies reporting factors associated with overall pneumococcal nasopharyngeal carriage in healthy, community-based study populations were eligible for inclusion. Two researchers independently reviewed studies to determine eligibility. Results are presented as narrative summaries. This review is registered with PROSPERO, CRD42020186914. Eighty-two studies were included, and 46 (56%) were conducted in LMICs. There was heterogeneity in the factors assessed in each study. Factors positively associated with pneumococcal carriage in all income classification were young age, ethnicity, symptoms of respiratory tract infection, childcare attendance, living with young children, poverty, exposure to smoke, season, and co-colonisation with other pathogens. Breastfeeding and antibiotic use were protective against carriage in all income classifications. Median (interquartile range) pneumococcal carriage rates differed by income classification, ranging from 51% (19.3-70.2%), 38.5% (19.3-51.6%), 31.5% (19.0-51.0%), 28.5% (16.8-35.4%), (P = 0.005) in low-, lower-middle, upper-middle, and high-income classifications, respectively. Our findings suggest that where measured, factors associated with pneumococcal nasopharyngeal carriage are similar across income classifications, despite the highest pneumococcal carriage rates being in low-income classifications. Reducing viral transmission through vaccination and public health interventions to address social determinants of health would play an important role.

Project description:BackgroundPrior studies have demonstrated hyporesponsiveness to pneumococcal conjugate vaccines (PCVs) when administered in the presence of homologous carriage. This may be substantially more important in Africa where carriage prevalence is high. Deriving a correlate of protection (CoP) for carriage is important in guiding the future use of extended PCVs as population control of pneumococcal disease by vaccination is now focused principally on its indirect effect. We therefore explored the complex relationship between existing carriage and vaccine responsiveness, and between serum IgG levels and risk of acquisition.MethodsWe undertook secondary analyses of data from two previously published clinical trials of the safety and immunogenicity of PCV in Kenya. We compared responses to vaccination between serotype-specific carriers and non-carriers at vaccination. We assessed the risk of carriage acquisition in relation to PCV-induced serum IgG levels using either a step- or continuous-risk function.ResultsFor newborns, the immune response among carriers was 51-82% lower than that among non-carriers, depending on serotype. Among toddlers, for serotypes 6B, 14 and 19F the post-vaccination response among carriers was lower by between 29 and 70%. The estimated CoP against acquisition ranged from 0.26 to 1.93μg/mL across serotypes, however, these thresholds could not be distinguished statistically from a model with constant probability of carriage independent of assay value.ConclusionWe have confirmed hyporesponsiveness in an equatorial African setting in both infants and toddlers. Population responses to vaccination are likely to improve with time as carriage prevalence of vaccine serotypes is reduced. We have not found clear correlates of protection against carriage acquisition among toddlers in this population. Assessing the potential of new vaccines through the use of CoP against carriage is still difficult as there are no clear-cut serotype specific correlates.

Project description:BackgroundIntroduction of pneumococcal vaccines in Nigeria is a priority as part of the Accelerated Vaccine Introduction Initiative (AVI) of the Global Alliance for Vaccines and Immunisation (GAVI). However, country data on the burden of pneumococcal disease (IPD) is limited and coverage by available conjugate vaccines is unknown. This study was carried out to describe the pre vaccination epidemiology and population biology of pneumococcal carriage in Nigeria.MethodsThis was a cross sectional survey. Nasopharyngeal swabs (NPS) were obtained from a population sample in 14 contiguous peri-urban Nigerian communities. Data on demographic characteristics and risk factor for carriage were obtained from all study participants. Pneumococci isolated from NPS were characterised by serotyping, antimicrobial susceptibility and Multi Locus Sequencing Typing (MLST).ResultsThe prevalence of pneumococcal carriage was 52.5%. Carriage was higher in children compared to adults (67.4% vs. 26%), highest (≈90%) in infants aged <9 months and reduced significantly with increasing age (P<0.001). Serotypes 19F (18.6%) and 6A (14.4%) were most predominant. Potential vaccine coverage was 43.8%, 45.0% and 62% for PCV-7, PCV-10 and PCV-13 respectively. There were 16 novel alleles, 72 different sequence types (STs) from the isolates and 3 Sequence Types (280, 310 and 5543) were associated with isolates of more than one serotype indicative of serotype switching. Antimicrobial resistance was high for cotrimoxazole (93%) and tetracycline (84%), a third of isolates had intermediate resistance to penicillin. Young age was the only risk factor significantly associated with carriage.ConclusionsPneumococcal carriage and serotype diversity is highly prevalent in Nigeria especially in infants. Based on the coverage of serotypes in this study, PCV-13 is the obvious choice to reduce disease burden and prevalence of drug resistant pneumococci. However, its use will require careful monitoring. Our findings provide sound baseline data for impact assessment following vaccine introduction in Nigeria.

Dataset Information

Modulation of nasopharyngeal innate defenses by viral coinfection predisposes individuals to experimental pneumococcal carriage.

Publications

Modulation of nasopharyngeal innate defenses by viral coinfection predisposes individuals to experimental pneumococcal carriage.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets