title: Analysis of humoral and phagocytic defenses against Streptococcus pneumoniae serotypes 1 and 3.
abstract: To better define relationships among pneumococcal anticapsular antibodies, opsonophagocytosis, and in vivo mouse protection, we measured these functions in sera from healthy individuals who had not received pneumococcal vaccine. For serotype 1 pneumococci, the level of antibody measured by radioimmunoassay did not predict mouse protection, as has been noted by others. For some sera, opsonic requirements for antibody and complement could be clearly demonstrated and a strong correlation obtained between concentration of antibody and degree of phagocytic killing. However, for most sera, antibody concentration did not correlate with opsonic activity, as measured by phagocytic bactericidal assay or uptake of radiolabeled bacteria. Sera with high concentrations of anticapsular antibody did not always support in vitro bacterial killing by leukocytes. Conversely, highly opsonic sera did not necessarily have substantial levels of measurable antibody. Moreover, in vitro opsonophagocytic activity failed to predict in vivo protection; sera could be opsonic in vitro but not protective in vivo and vice versa. For serotype 3 pneumococci, antibody concentrations correlated strongly with mouse protective titers, as has been noted by others for type 3. Opsonophagocytosis, as measured by leukocyte bactericidal activity, required both complement and heat-stable substance(s) present in high-antibody sera, presumably antibody. Furthermore, increasing concentrations of serum enhanced phagocytic killing in a fashion that could be correlated with anticapsular antibody content. However, correlation with opsonophagocytosis was not so strong as with mouse protection, and there was no correlation between antibody concentration and opsonization as measured by uptake of radiolabeled bacteria. These observations suggest that opsonophagocytosis (with the definitive end point of bacterial killing) cannot be the standard against which to measure antibody concentrations. Furthermore, host protective mechanisms against pneumococci remain to be clearly defined. Even if opsonization by anticapsular antibody is the primary mechanism, there is need for development of improved functional assays of protection.
authors.affiliation: Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City.
authors.forename: D P
authors.initials: DP
authors.lastname: Fine
authors.forename: J L
authors.initials: JL
authors.lastname: Kirk
authors.forename: G
authors.initials: G
authors.lastname: Schiffman
authors.forename: J E
authors.initials: JE
authors.lastname: Schweinle
authors.forename: J C
authors.initials: JC
authors.lastname: Guckian
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis; D000917:Antibody Formation; D001770:Blood Bactericidal Activity; D006801:Humans; D051379:Mice; D010587:Phagocytosis; D011008:Pneumococcal Infections / Q000276:immunology*; D013296:Streptococcus pneumoniae
chemical_list: D000907:Antibodies, Bacterial