title: Effect of Haemophilus influenzae polysaccharide outer membrane protein complex conjugate vaccine on macrophages.
abstract: Haemophilus influenzae type b polysaccharide-conjugate vaccines elicit protective antibody responses in young infants. One of these conjugates, polysaccharide linked to outer membrane protein complex (PRP-OMPC), is produced by linking the capsular polysaccharide to an outer membrane protein complex derived from group B Neisseria meningitidis. The outer membrane protein complex contains T cell carrier epitopes that elicit T cell-dependent antibody responses. OMPC also has been shown to increase the antibody response to other proteins administered concurrently that are not covalently linked (i.e., acts as an adjuvant). In this study PRP-OMPC immunized mice demonstrated significant increases in spleen size as well as in splenocyte number as compared to saline controls (p < 0.01, p < 0.001, respectively). No such increase was noted after immunization with another H. influenzae type b-conjugate vaccine, oligosaccharide linked to a variant of diphtheria toxin. By analytic flow cytometry, the mice immunized with PRP-OMPC demonstrated an increase in large splenocytes expressing the Ag Mac-1 (CD11b, CR3). Furthermore, the spleens on histologic examination were characterized by an increase in the red pulp area consisting predominantly of cells of macrophage morphology. By immunohistochemical staining, the cells were identified as macrophages due to expression of Mac-1 and p150,95 (CD11C) Ag. After PRP-OMPC immunization, severe combined immunodeficient mice also demonstrated significant splenomegaly with an increase in macrophages identified by expression of Mac-1 and MHC class II Ag. Thus PRP-OMPC vaccine resulted in T cell-independent splenomegaly with an increase number of macrophages. We propose that this unique property may confer increased immunogenicity to PRP-OMPC through macrophage activation and cytokine release. Furthermore, the effect on macrophages may explain the "adjuvant" capacity of OMPC.
authors.affiliation: Laboratory of Infectious Diseases, Dana-Farber Cancer Institute, Boston, MA 02115.
authors.forename: D M
authors.initials: DM
authors.lastname: Ambrosino
authors.forename: D
authors.initials: D
authors.lastname: Bolon
authors.forename: H
authors.initials: H
authors.lastname: Collard
authors.forename: R
authors.initials: R
authors.lastname: Van Etten
authors.forename: M V
authors.initials: MV
authors.lastname: Kanchana
authors.forename: R W
authors.initials: RW
authors.lastname: Finberg
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000494:pharmacology*; D001428:Bacterial Vaccines / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003602:Cytotoxicity, Immunologic; D004168:Diphtheria Toxoid / Q000494:pharmacology; D004306:Dose-Response Relationship, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D018073:Haemophilus Vaccines; D007074:Immunoglobulin G / Q000096:biosynthesis; D016167:Integrin alphaXbeta2; D007694:Killer Cells, Natural / Q000276:immunology; D016177:Macrophage-1 Antigen / Q000096:biosynthesis; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D016513:Mice, SCID; D011135:Polysaccharides, Bacterial / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013601:T-Lymphocytes / Q000276:immunology; D014611:Vaccination; D014614:Vaccines, Synthetic / Q000494:pharmacology*
chemical_list: D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D004168:Diphtheria Toxoid; D018073:Haemophilus Vaccines; C052180:Haemophilus influenzae type b-polysaccharide vaccine-diphtheria toxoid conjugate; C061964:Haemophilus influenzae-type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine; D007074:Immunoglobulin G; D016167:Integrin alphaXbeta2; D016177:Macrophage-1 Antigen; D011135:Polysaccharides, Bacterial; D014614:Vaccines, Synthetic