Naturally Acquired Human Immunity to Pneumococcus Is Dependent on Antibody to Protein Antigens

Wilson, Robert, Cohen, Jonathan M., Reglinski, Mark, Jose, Ricardo J., Chan, Win Yan, Marshall, Helina, de Vogel, Corné, Gordon, Stephen ORCID: https://orcid.org/0000-0001-6576-1116, Goldblatt, David, Petersen, Fernanda C., Baxendale, Helen and Brown, Jeremy S. (2017) 'Naturally Acquired Human Immunity to Pneumococcus Is Dependent on Antibody to Protein Antigens'. PLoS Pathogens, Vol 13, Issue 1, e1006137.

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Abstract

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.

Item Type:	Article
Subjects:	QU Biochemistry > Proteins. Amino Acids. Peptides > QU 55 Proteins QW Microbiology and Immunology > Immunity by Type > QW 541 Natural immunity. Immunogenetics QW Microbiology and Immunology > Antigens and Antibodies. Toxins and Antitoxins > QW 573 Antigens QW Microbiology and Immunology > Antigens and Antibodies. Toxins and Antitoxins > QW 575 Antibodies WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 217 Pneumococcal infections
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department
Digital Object Identifer (DOI):	https://doi.org/10.1371/journal.ppat.1006137
SWORD Depositor:	JISC Pubrouter
Depositing User:	JISC Pubrouter
Date Deposited:	15 Feb 2017 14:25
Last Modified:	07 Oct 2019 08:24
URI:	https://archive.lstmed.ac.uk/id/eprint/6780

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