期刊
PLOS PATHOGENS
卷 13, 期 1, 页码 -出版社
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.ppat.1006137
关键词
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资金
- Department of Health's NIHR Biomedical Research Centre
- UCL
- NIHR
- Academy of Medical Sciences
- Wellcome Trust
- MRC
- BBSRC
- Meningitis NOW project grant
- Academy of Medical Sciences (AMS) [AMS-SGCL5-Cohen] Funding Source: researchfish
- Biotechnology and Biological Sciences Research Council [1209467] Funding Source: researchfish
- Medical Research Council [1130652] Funding Source: researchfish
- National Institute for Health Research [ACF-2009-18-029, CL-2009-18-010] Funding Source: researchfish
Naturally acquired immunity against invasive pneumococcal disease (IPD) is thought to be dependent on anti-capsular antibody. However nasopharyngeal colonisation by Streptococcus pneumoniae also induces antibody to protein antigens that could be protective. We have used human intravenous immunoglobulin preparation (IVIG), representing natural IgG responses to S. pneumoniae, to identify the classes of antigens that are functionally relevant for immunity to IPD. IgG in IVIG recognised capsular antigen and multiple S. pneumoniae protein antigens, with highly conserved patterns between different geographical sources of pooled human IgG. Incubation of S. pneumoniae in IVIG resulted in IgG binding to the bacteria, formation of bacterial aggregates, and enhanced phagocytosis even for unencapsulated S. pneumoniae strains, demonstrating the capsule was unlikely to be the dominant protective antigen. IgG binding to S. pneumoniae incubated in IVIG was reduced after partial chemical or genetic removal of bacterial surface proteins, and increased against a Streptococcus mitis strain expressing the S. pneumoniae protein PspC. In contrast, depletion of type-specific capsular antibody from IVIG did not affect IgG binding, opsonophagocytosis, or protection by passive vaccination against IPD in murine models. These results demonstrate that naturally acquired protection against IPD largely depends on antibody to protein antigens rather than the capsule.
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