Matches in SemOpenAlex for { <https://semopenalex.org/work/W2090586504> ?p ?o ?g. }
Showing items 1 to 84 of
84
with 100 items per page.
- W2090586504 abstract "Preventing Streptococcus pneumoniae lung infections will have substantial health benefits, yet existing polysaccharide vaccines are not effective against pneumonia. Identifying the mechanisms of naturally-acquired immunity to S. pneumoniae lung infections could indicate alternative preventative strategies. Human intravenous immunoglobulin (IVIG) preparations pooled from >1000 donors prevent respiratory infections in patients with hypogammaglobuniaemia. IVIG therefore provides a tool to investigate the naturally-acquired antibody responses to S. pneumoniae within a population. We have used mouse models and in vitro assays to assess the efficacy of IVIG for preventing S. pneumoniae lung infections and to identify the immunodominant target antigens. In a mouse pneumonia model, IVIG treatment was highly protective against bacteraemia (17% septicaemia v. 100% in controls, P = 0.015) and partially protected against lung infection (lung CFU log 10 3.7 for IVIG v. 6.3 for controls, P = 0.041) but not against nasopharyngeal colonisation. Depletion of phagocyte subsets demonstrated that IVIG-mediated protection required neutrophils and macrophages for lungs and blood respectively. Flow-cytometry assays demonstrated that IgG within IVIG preparations opsonised S. pneumoniae effectively. Importantly, IgG opsonisation was reduced by pre-treatment of bacteria with pronase to remove bacterial surface proteins but not by depletion of anti-capsular antibody. Furthermore, in vitro assays demonstrated that IVIG facilitated phagocytosis, growth impairment and bacterial agglutination of capsule-deficient S. pneumoniae mutants, in mice IVIG depleted of anti-capsular antibody remained protective against lung infection and septicaemia. These results demonstrate that surface proteins rather than the capsule are targets for naturally-acquired adaptive immunity to S. pneumoniae . The potential S. pneumoniae protein antigen targets in IVIG were assessed using a semi-quantitative assay against 18 recombinant pneumococcal proteins. The results demonstrated significant IgG responses to the conserved pneumococcal protein antigens PhtD, PspC, PspA and PsaA. Interestingly, antibody titres to some of these antigens were reduced in sera from elderly compared to younger subjects, potentially identifying people at higher risk of S. pneumoniae infection. Our data demonstrate that the accepted paradigm that naturally-acquired immunity to S. pneumoniae depends on anti-capsular antigen is inaccurate, and instead antibody to proteins is dominant. These data will allow better evaluation of those at risk of S. pneumoniae infection and improved vaccine design." @default.
- W2090586504 created "2016-06-24" @default.
- W2090586504 creator A5013390528 @default.
- W2090586504 creator A5026879533 @default.
- W2090586504 creator A5031412055 @default.
- W2090586504 creator A5043963885 @default.
- W2090586504 creator A5056568993 @default.
- W2090586504 creator A5058129814 @default.
- W2090586504 creator A5071750927 @default.
- W2090586504 creator A5020137642 @default.
- W2090586504 date "2013-11-14" @default.
- W2090586504 modified "2023-09-27" @default.
- W2090586504 title "P238 Role of naturally-acquired IgG in protection from S. pneumoniae lung infection" @default.
- W2090586504 doi "https://doi.org/10.1136/thoraxjnl-2013-204457.390" @default.
- W2090586504 hasPublicationYear "2013" @default.
- W2090586504 type Work @default.
- W2090586504 sameAs 2090586504 @default.
- W2090586504 citedByCount "0" @default.
- W2090586504 crossrefType "journal-article" @default.
- W2090586504 hasAuthorship W2090586504A5013390528 @default.
- W2090586504 hasAuthorship W2090586504A5020137642 @default.
- W2090586504 hasAuthorship W2090586504A5026879533 @default.
- W2090586504 hasAuthorship W2090586504A5031412055 @default.
- W2090586504 hasAuthorship W2090586504A5043963885 @default.
- W2090586504 hasAuthorship W2090586504A5056568993 @default.
- W2090586504 hasAuthorship W2090586504A5058129814 @default.
- W2090586504 hasAuthorship W2090586504A5071750927 @default.
- W2090586504 hasBestOaLocation W20905865041 @default.
- W2090586504 hasConcept C126322002 @default.
- W2090586504 hasConcept C159654299 @default.
- W2090586504 hasConcept C203014093 @default.
- W2090586504 hasConcept C2777714996 @default.
- W2090586504 hasConcept C2777914695 @default.
- W2090586504 hasConcept C2779341262 @default.
- W2090586504 hasConcept C2781253189 @default.
- W2090586504 hasConcept C2908647359 @default.
- W2090586504 hasConcept C501593827 @default.
- W2090586504 hasConcept C71924100 @default.
- W2090586504 hasConcept C86803240 @default.
- W2090586504 hasConcept C8891405 @default.
- W2090586504 hasConcept C89423630 @default.
- W2090586504 hasConcept C99454951 @default.
- W2090586504 hasConceptScore W2090586504C126322002 @default.
- W2090586504 hasConceptScore W2090586504C159654299 @default.
- W2090586504 hasConceptScore W2090586504C203014093 @default.
- W2090586504 hasConceptScore W2090586504C2777714996 @default.
- W2090586504 hasConceptScore W2090586504C2777914695 @default.
- W2090586504 hasConceptScore W2090586504C2779341262 @default.
- W2090586504 hasConceptScore W2090586504C2781253189 @default.
- W2090586504 hasConceptScore W2090586504C2908647359 @default.
- W2090586504 hasConceptScore W2090586504C501593827 @default.
- W2090586504 hasConceptScore W2090586504C71924100 @default.
- W2090586504 hasConceptScore W2090586504C86803240 @default.
- W2090586504 hasConceptScore W2090586504C8891405 @default.
- W2090586504 hasConceptScore W2090586504C89423630 @default.
- W2090586504 hasConceptScore W2090586504C99454951 @default.
- W2090586504 hasLocation W20905865041 @default.
- W2090586504 hasLocation W20905865042 @default.
- W2090586504 hasOpenAccess W2090586504 @default.
- W2090586504 hasPrimaryLocation W20905865041 @default.
- W2090586504 hasRelatedWork W1791691667 @default.
- W2090586504 hasRelatedWork W1934805527 @default.
- W2090586504 hasRelatedWork W1954011932 @default.
- W2090586504 hasRelatedWork W1989073547 @default.
- W2090586504 hasRelatedWork W2057576654 @default.
- W2090586504 hasRelatedWork W2075453664 @default.
- W2090586504 hasRelatedWork W2075917748 @default.
- W2090586504 hasRelatedWork W2104547218 @default.
- W2090586504 hasRelatedWork W2109594331 @default.
- W2090586504 hasRelatedWork W2142890591 @default.
- W2090586504 hasRelatedWork W2146846054 @default.
- W2090586504 hasRelatedWork W2155161315 @default.
- W2090586504 hasRelatedWork W2159323999 @default.
- W2090586504 hasRelatedWork W2400724561 @default.
- W2090586504 hasRelatedWork W2412438632 @default.
- W2090586504 hasRelatedWork W2556154257 @default.
- W2090586504 hasRelatedWork W2752449863 @default.
- W2090586504 hasRelatedWork W2795694182 @default.
- W2090586504 hasRelatedWork W2799816271 @default.
- W2090586504 hasRelatedWork W3200219217 @default.
- W2090586504 isParatext "false" @default.
- W2090586504 isRetracted "false" @default.
- W2090586504 magId "2090586504" @default.
- W2090586504 workType "article" @default.