Naturally Acquired Human Immunity to Pneumococcus Is Dependent on Antibody to Protein Antigens.
Robert WilsonJonathan M CohenMark ReglinskiRicardo J JoseWin Yan ChanHelina MarshallCorné de VogelStephen GordonDavid GoldblattFernanda C PetersenHelen BaxendaleJeremy Stuart BrownPublished in: PLoS pathogens (2017)
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.
Keyphrases
- endothelial cells
- dendritic cells
- protein protein
- escherichia coli
- amino acid
- respiratory tract
- induced pluripotent stem cells
- clinical trial
- transcription factor
- small molecule
- magnetic resonance
- magnetic resonance imaging
- high dose
- mass spectrometry
- molecularly imprinted
- candida albicans
- liquid chromatography
- placebo controlled