title: Efficacy of opsonic and nonopsonic serotype 3 pneumococcal capsular polysaccharide-specific monoclonal antibodies against intranasal challenge with Streptococcus pneumoniae in mice.
abstract: Serotype-specific antibodies to pneumococcal capsular polysaccharide (PPS) are a critical component of vaccine-mediated immunity to Streptococcus pneumoniae. In this study, we investigated the in vitro opsonophagocytic activities of three PPS-specific mouse immunoglobulin G1 monoclonal antibodies (MAbs), 1E2, 5F6, and 7A9, and determined their in vivo efficacies against intranasal challenge with WU2, a serotype 3 pneumococcal strain, in normal and immunodeficient mice. The MAbs had different in vitro activities in a pneumococcal killing assay: 7A9 enhanced killing by mouse neutrophils and J774 cells in the presence of a complement source, whereas 5F6 promoted killing in the absence, but not the presence, of complement, and 1E2 did not promote killing under any conditions. Nonetheless, all three MAbs protected normal and complement component 3-deficient mice from a lethal intranasal challenge with WU2 in passive-immunization experiments in which 10 mug of the MAbs were administered intraperitoneally before intranasal challenge. In contrast, only 1E2 protected Fcgamma receptor IIB knockout (FcgammaRIIB KO) mice and mice that were depleted of neutrophils with the MAb RB6, whereas 7A9 and 5F6 required neutrophils and FcgammaRIIB to mediate protection. Conversely, 7A9 and 5F6 protected FcgammaR KO mice, but 1E2 did not. Hence, the efficacy of 1E2 required an activating FcgammaR(s), whereas 5F6 and 7A9 required the inhibitory FcgammaR (FcgammaRIIB). Taken together, our data demonstrate that both MAbs that do and do not promote pneumococcal killing in vitro can mediate protection in vivo, although their efficacies depend on different host receptors and/or components.
authors.affiliation: Division of Infectious Diseases, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Haijun
authors.initials: H
authors.lastname: Tian
authors.forename: Sarah
authors.initials: S
authors.lastname: Weber
authors.forename: Peter
authors.initials: P
authors.lastname: Thorkildson
authors.forename: Thomas R
authors.initials: TR
authors.lastname: Kozel
authors.forename: Liise-Anne
authors.initials: LA
authors.lastname: Pirofski
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000627:therapeutic use; D000918:Antibody Specificity; D016667:Bacterial Capsules / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000627:therapeutic use; D051379:Mice; D008810:Mice, Inbred C57BL; D009895:Opsonin Proteins / Q000276:immunology / Q000378:metabolism; D010587:Phagocytosis; D011008:Pneumococcal Infections / Q000276:immunology / Q000382:microbiology / Q000401:mortality / Q000517:prevention & control*; D012703:Serotyping; D013296:Streptococcus pneumoniae / Q000145:classification / Q000276:immunology / Q000472:pathogenicity*; D016896:Treatment Outcome
chemical_list: D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D007074:Immunoglobulin G; D009895:Opsonin Proteins