Aggregation of Streptococcus pneumoniae by a Pneumococcal Capsular Polysaccharide-Specific Human Monoclonal IgM Correlates with Antibody Efficacy In Vivo
- 1 May 2010
- journal article
- Published by American Society for Microbiology in Clinical and Vaccine Immunology
- Vol. 17 (5), 713-721
- https://doi.org/10.1128/cvi.00410-09
Abstract
Acquired antibody immunity to Streptococcus pneumoniae (pneumococcus) has been linked to serotype (ST)-specific opsonic antibodies to the relevant pneumococcal capsular polysaccharide (PPS) that mediate protection by enhancing the bactericidal effect of host phagocytes. Despite the well-recognized role of opsonic IgG in host defense against pneumococcus, PPS-specific monoclonal antibodies (MAbs) that mediate protection against lethal challenge with ST3 pneumococcus in mice but do not promote phagocytic killing in vitro (nonopsonic antibodies) have been described. In this study, we sought to determine the biological activity of one such MAb, A7 (a human PPS3-specific IgM), and the mechanism by which it mediates protection. In vitro studies demonstrated that coincubation of A7 with ST3 in the absence of phagocytes or a complement source resulted in a reduction in CFU on blood agar plates that was largely reversible by sonication. A chromogenic cellular proliferation assay demonstrated that A7 did not affect replication of ST3 in liquid culture. The ability of A7 to induce aggregation of ST3 was confirmed by fluorescence microscopy and flow cytometry: A7 induced aggregation of ST3, and in the presence of a complement source, A7 promoted deposition of complement component 3 (C3) on aggregated bacteria in a dose-dependent fashion. Similarly, administration of preincubated mixtures of A7 and ST3 intraperitoneally to mice protected them from the lethality of ST3 in a dose-dependent fashion. These findings suggest that A7-mediated aggregation enhances resistance to ST3, most likely by enhancing C3 deposition on the ST3 capsule, thereby promoting host antipneumococcal activity in vivo.Keywords
This publication has 62 references indexed in Scilit:
- Characterization of Protective Mucosal and Systemic Immune Responses Elicited by Pneumococcal Surface Protein PspA and PspC Nasal Vaccines against a Respiratory Pneumococcal Challenge in MiceClinical and Vaccine Immunology, 2009
- Efficacy of Opsonic and Nonopsonic Serotype 3 Pneumococcal Capsular Polysaccharide-Specific Monoclonal Antibodies against Intranasal Challenge withStreptococcus pneumoniaein MiceInfection and Immunity, 2009
- Structural requirements for the interaction of human IgM and IgA with the human Fc alpha/mu receptorEuropean Journal of Immunology, 2009
- Antibody to the Type 3 Capsule Facilitates Immune Adherence of Pneumococci to Erythrocytes and Augments Their Transfer to MacrophagesInfection and Immunity, 2009
- Pneumococcal Necrotizing Pneumonia in Utah: Does Serotype Matter?Clinical Infectious Diseases, 2008
- PspA and PspC Minimize Immune Adherence and Transfer of Pneumococci from Erythrocytes to Macrophages through Their Effects on Complement ActivationInfection and Immunity, 2007
- An Anti-β-Glucan Monoclonal Antibody Inhibits Growth and Capsule Formation of Cryptococcus neoformans In Vitro and Exerts Therapeutic, Anticryptococcal Activity In VivoInfection and Immunity, 2007
- Impact of the Molecular Form of Immunoglobulin A on Functional Activity in Defense againstStreptococcus pneumoniaeInfection and Immunity, 2007
- Functional Antibodies Elicited by Two Heptavalent Pneumococcal Conjugate Vaccines in the Finnish Otitis Media Vaccine TrialInfection and Immunity, 2007
- A Human Monoclonal Immunoglobulin M Reduces Bacteremia and Inflammation in a Mouse Model of Systemic Pneumococcal InfectionClinical and Vaccine Immunology, 2007