Publications (2)4.41 Total impact
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ABSTRACT: The aim of the study was to determine the concentration of pneumococcal antibodies after a dose of 7-valent pneumococcal conjugate vaccine (PCV7) in 30 asplenic children between 4 months and 19 years of age. Fifteen children had received pneumococcal polysaccharide vaccine (PPV) approximately 5 years prior to vaccination with PCV7. The antibody concentrations against serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F were measured by ELISA before and after the PCV7 vaccination. Before vaccination with PCV7, the antibody concentrations were similar in children who had or had not received PPV previously. A dose of PCV7 stimulated a good immune response in asplenic patients. Prior immunization with PPV did not affect the antibody concentration after the vaccination with PCV7. In conclusion, asplenic children vaccinated with PPV may need revaccination with PPV earlier than the recommended 3-5 years after the first dose. PCV7 induces a satisfactory immune response in asplenic patients and should be considered as an alternative vaccine in that patient group.
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ABSTRACT: Bacteria-specific IgA antibodies are efficient opsonins for neutrophils and mononuclear phagocytes, provided that the phagocytes express the Fca receptor (CD89). Expression of CD89 can be stimulated by inflammatory cytokines, activated complement factors and certain microbial components. In one study, unstimulated phagocytes were able to ingest IgA antibody-treated pneumococci, but only in the presence of complement, which was found to be activated by the IgA antibodies along the alternative pathway. Pneumococci produce IgA1 protease that cleaves human IgA1, but not IgA2, molecules in the hinge region. This leaves IgA1 as Fabα (monovalent) deprived of Fcα which contains the docking site for CD89. IgA1 is the vastly predominant subclass of IgA in the upper airways and circulation of humans. Aims: To examine the effects of IgA1 protease activity and complement on phagocytosis of IgA antibody-coated pneumococci by an unstimulated human phagocytic cell line (hl60). Materials and methods: IgA1 and IgA2 monoclonal antibodies to serotype 4 pneumococcal capsular polysaccharide (ps) were generated by heterohybridoma technique involving B cells from human vaccinees. Isogenic serotype 4 pneumococci with and without IgA1 protease activity, respectively, were obtained after inactivation of the iga gene of the TIGR4 strain. Opsonophagocytosis was quantitated using the assay described by Romero-Steiner et al. Based on enumeration of surviving bacteria by culture. The integrity of IgA molecules was examined by western blotting. Results: Both IgA1 and IgA2 antibody to type-4 polysaccharide-induced phagocytosis of IgA1 protease-deficient type-4 pneumococci equally well in the absence as in the presence of complement. Iga1 antibody to type-4 polysaccharide displayed a fourfold higher opsonophagocytosis titer against IgA1 protease deficient compared to homologous wildtype target bacteria. A similar effect of IgA1 protease activity of the target bacteria was not observed in a parallel experiment where IgA2 antibody to type-4 polysaccharide served as opsonin. IgA1 antibody extracted from IgA1 protease-producing target bacteria was almost exclusively in the form of Fabα. Conversely, IgA1 from protease-deficient bacteria and IgA2 from both types of bacteria were intact. Conclusions: These results indicate that the IgA1 protease activity of S. neumoniae may help the bacteria escape IgA1 antibody-mediated opsonophagocytosis. Besides, in these experiments, IgA-mediated opsonophagocytosis was independent of complement.
National Public Health InstituteHelsinki, Southern Finland Province, Finland