title: Vaccine-induced human antibody responses to the Haemophilus influenzae b polysaccharide in severe combined immunodeficient mice engrafted with human leukocytes.
abstract: We examined the ability of severe combined immunodeficient (SCID) mice-human peripheral blood leukocyte (PBL) chimeras to respond to immunization with Haemophilus influenzae b polysaccharide (Hib PS) vaccines. Two to 3 wk after PBL engraftment, human-PBL-SCID mice, prepared with PBL from one of five adult donors, were immunized with free or protein-conjugated Hib PS. Antibody to Hib PS was quantitated in preimmunization and postimmunization sera. Before immunization, anti-Hib PS antibody was detectable (greater than 10 ng/mL) in three of 40 mice. Of the 37 human-PBL-SCID mice not having detectable serum antibody before immunization, 31 produced greater than or equal to 20 ng/mL (greater than or equal to 2-fold increase) anti-Hib PS antibody 2 to 3 wk after immunization. Both free and protein-conjugated forms of Hib PS were immunogenic. Geometric mean anti-Hib PS antibody levels ranged from 50 to 139 ng/mL. Vaccine-induced anti-Hib PS antibodies frequently expressed HibId-1, a cross-reactive idiotype that predominates the in vivo human antibody response to Hib PS. However, among mice engrafted with PBL from a single donor, the HibId-1 distribution was highly skewed, suggesting that clonally distinct B cells were being stimulated in individual mice. These findings indicate that human PBL transplanted into SCID mice are functionally responsive to Hib PS antigenic challenge. This system may serve as a useful model for studying the regulation and cellular requirements for human polysaccharide immunity.
authors.affiliation: Children's Hospital Oakland Research Institute, California 94609.
authors.forename: A H
authors.initials: AH
authors.lastname: Lucas
authors.forename: T E
authors.initials: TE
authors.lastname: Siff
authors.forename: K H
authors.initials: KH
authors.lastname: Trujillo
authors.forename: M Y
authors.initials: MY
authors.lastname: Kitamura
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D016667:Bacterial Capsules; D001428:Bacterial Vaccines / Q000276:immunology*; D002678:Chimera; D018073:Haemophilus Vaccines; D006193:Haemophilus influenzae / Q000276:immunology*; D006801:Humans; D017708:Leukocyte Transfusion; D007962:Leukocytes / Q000276:immunology; D051379:Mice; D016513:Mice, SCID; D008954:Models, Biological; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D016511:Severe Combined Immunodeficiency / Q000276:immunology*; D014183:Transplantation, Heterologous
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D018073:Haemophilus Vaccines; C044237:Haemophilus influenzae type b polysaccharide vaccine; D011135:Polysaccharides, Bacterial