title: Streptococcus pneumoniae capsular serotype 19F is more resistant to C3 deposition and less sensitive to opsonophagocytosis than serotype 6B.
abstract: The polysaccharide capsule is a major virulence mechanism of Streptococcus pneumoniae, shielding the bacterium from phagocytes. Capsule types may differ in their abilities to resist immune defense. Antibody-mediated complement activation and opsonophagocytosis are crucial in protection against pneumococcus. Conjugate vaccine trials suggest imperfect protection against 19F. We have previously shown that significantly more anti-19F than anti-6B antibody is needed for killing in the opsonophagocytic assay (OPA). In this study, we explored whether the amount of C3 deposited on serotype 6B and 19F pneumococcal strains reflects their sensitivity to opsonophagocytosis. We compared clinical 6B and 19F nasopharyngeal, middle ear, and blood isolates as well as reference OPA strains (n = 16) for their sensitivity to opsonophagocytosis and C3 deposition. Sixfold anticapsular antibody concentrations were required for 50% opsonophagocytic killing of 19F compared to that of 6B strains. Serotype 19F was more resistant to C3 deposition than 6B. Complement deposition and opsonophagocytosis were dependent on the concentration of anticapsular antibodies. Differences between pneumococcal serotypes in antibody-mediated protection may partly be explained by the abilities of the capsules to resist complement deposition. These findings support previous studies suggesting that higher antibody concentrations to the capsular polysaccharide are needed for protection against disease caused by serotype 19F than that caused by 6B.
authors.affiliation: National Public Health Institute, Department of Vaccines, Helsinki, Finland. merit.melin@ktl.fi
authors.forename: Merit
authors.initials: M
authors.lastname: Melin
authors.forename: Hanna
authors.initials: H
authors.lastname: Jarva
authors.forename: Lotta
authors.initials: L
authors.lastname: Siira
authors.forename: Seppo
authors.initials: S
authors.lastname: Meri
authors.forename: Helena
authors.initials: H
authors.lastname: Käyhty
authors.forename: Merja
authors.initials: M
authors.lastname: Väkeväinen
mesh_terms: D000907:Antibodies, Bacterial / Q000276:immunology; D016667:Bacterial Capsules / Q000502:physiology; D001426:Bacterial Proteins / Q000235:genetics / Q000378:metabolism; D003176:Complement C3 / Q000378:metabolism*; D017242:Complement Factor H / Q000378:metabolism; D015964:Gene Expression Regulation, Bacterial; D018922:HL-60 Cells; D006801:Humans; D009895:Opsonin Proteins; D010587:Phagocytosis / Q000502:physiology*; D011485:Protein Binding; D044967:Serum; D013296:Streptococcus pneumoniae / Q000145:classification* / Q000235:genetics / Q000502:physiology*
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D003176:Complement C3; D009895:Opsonin Proteins; C051592:pneumococcal surface protein A; D017242:Complement Factor H