title: Naturally Acquired HMW1- and HMW2-Specific Serum Antibodies in Adults and Children Mediate Opsonophagocytic Killing of Nontypeable Haemophilus influenzae.
abstract: The HMW1 and HMW2 proteins are highly immunogenic adhesins expressed by approximately 75% of nontypeable Haemophilus influenzae (NTHi) strains, and HMW1- and HMW2-specific antibodies can mediate opsonophagocytic killing of NTHi. In this study, we assessed the ability of HMW1- and HMW2-specific antibodies in sera from healthy adults and convalescent-phase sera from children with NTHi otitis media to mediate killing of homologous and heterologous NTHi. The serum samples were examined pre- and postadsorption on HMW1 and HMW2 affinity columns, and affinity-purified antibodies were assessed for ability to mediate killing of homologous and heterologous strains. Adult serum samples mediated the killing of six prototype NTHi strains at titers of <1:10 to 1:1,280. HMW1- and HMW2-adsorbed sera demonstrated unchanged to 8-fold decreased opsonophagocytic titers against the homologous strains. Each affinity-purified antibody preparation mediated the killing of the respective homologous strain at titers of <1:10 to 1:320 and of the five heterologous strains at titers of <1:10 to 1:320, with most preparations killing most heterologous strains to some degree. None of the acute-phase serum samples from children mediated killing, but each convalescent-phase serum sample mediated killing of the infecting strain at titers of 1:40 to 1:640. HMW1- and HMW2-adsorbed convalescent-phase serum samples demonstrated ≥4-fold decreases in titer. Three of four affinity-purified antibody preparations mediated killing of the infecting strain at titers of 1:20 to 1:320, but no killing of representative heterologous strains was observed. HMW1- and HMW2-specific antibodies capable of mediating opsonophagocytic killing are present in the serum from normal adults and develop in convalescent-phase sera of children with NTHi otitis media. Continued investigation of the HMW1 and HMW2 proteins as potential vaccine candidates for the prevention of NTHi disease is warranted.
authors.affiliation: Department of Pediatrics, St. Louis University School of Medicine, and the Pediatric Research Institute, Cardinal Glennon Children's Medical Center, St. Louis, Missouri, USA.
authors.forename: Linda E
authors.initials: LE
authors.lastname: Winter
authors.affiliation: Department of Pediatrics, St. Louis University School of Medicine, and the Pediatric Research Institute, Cardinal Glennon Children's Medical Center, St. Louis, Missouri, USA barenksj@slu.edu.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Barenkamp
mesh_terms: D018829:Adhesins, Bacterial / Q000276:immunology*; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood* / Q000276:immunology; D002648:Child; D006192:Haemophilus Infections / Q000276:immunology* / Q000382:microbiology; D006193:Haemophilus influenzae / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D007223:Infant; D009895:Opsonin Proteins / Q000276:immunology; D010033:Otitis Media / Q000382:microbiology; D010587:Phagocytosis
chemical_list: D018829:Adhesins, Bacterial; D000907:Antibodies, Bacterial; C117431:HMW1 protein, bacteria; C117432:HMW2 protein, bacteria; D009895:Opsonin Proteins