title: Safety and immunogenicity of haemophilus influenzae type B polysaccharide or conjugate vaccines in an elderly adult population.
abstract: OBJECTIVE
  To evaluate the safety and immunogenicity of unconjugated Haemophilus influenzae type b (Hib) polysaccharide (PRP) vaccine and two PRP-protein-conjugated vaccines as a model for the comparison of protein-conjugated versus plain polysaccharide vaccines in the elderly.
  
  
  METHODS
  Randomized, double-blind, prospective study.
  
  
  METHODS
  University-based center for vaccine research and development.
  
  
  METHODS
  A total of 125 adults, aged 64 to 92, who were judged to be in general good health and lacking any significant underlying medical conditions.
  
  
  METHODS
  Subjects were randomized to receive one of three vaccines: Group 1 (n=39), PRP; Group 2 (n=44), PRP conjugated to an outer-membrane protein complex of Neisseria meningitidis (PRP-OMP); and Group 3 (n=42), PRP conjugated to diphtheria toxoid (PRP-D). Sera were obtained before immunization and 1 and 12 months later.
  
  
  METHODS
  Subjects maintained a diary of injection site and systemic reactions for 3 days after immunization. A radioantigen-binding assay was used to measure total concentrations of serum anticapsular antibody, and an enzyme-linked immunosorbent assay was used to measure immunoglobulin (Ig) G1 and IgG2 anticapsular antibody responses. Antibody functional activity was assessed using a complement-mediated bactericidal assay.
  
  
  RESULTS
  Before vaccination, the geometric mean serum anticapsular antibody concentration was 0.8 microg/mL, but fewer than 10% of subjects had detectable bactericidal activity (titer>1:4). The magnitude, subclass distribution, and bactericidal activity of antibody responses to unconjugated PRP vaccine were similar to those observed in previous studies of younger adults immunized with PRP. The OMP conjugate, which is highly immunogenic after one dose in 2-month old infants, did not elicit anticapsular antibody responses in the elderly greater than those elicited by PRP vaccine (P=.43). In contrast, the D conjugate, which is poorly immunogenic in 2-month old infants, elicited higher anticapsular antibody responses than PRP vaccine in the elderly (P=.01) and higher levels than the OMP-conjugate 1 year after vaccination (P<.006).
  
  
  CONCLUSIONS
  Elderly adults develop protective anticapsular antibody responses to unconjugated and conjugated PRP vaccine. The higher anticapsular antibody responses to the D conjugate but not to the OMP conjugate in the elderly, which is the reverse of that observed in immunized infants, implies fundamental differences in the immunological mechanisms by which the two age groups respond to PRP and by which the OMP and D conjugates elicit anticapsular antibody responses.
authors.affiliation: Department of Internal Medicine, Division of Infectious Diseases and Immunology, Saint Louis University Health Science Center, 3635 Vista Avenue at Grand, PO Box 15250, Saint Louis, MO 63110, USA. lottenkr@slu.edu
authors.forename: Kathleen R
authors.initials: KR
authors.lastname: Lottenbach
authors.forename: Dan M
authors.initials: DM
authors.lastname: Granoff
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Barenkamp
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Powers
authors.forename: Donald
authors.initials: D
authors.lastname: Kennedy
authors.forename: Sharon
authors.initials: S
authors.lastname: Irby-Moore
authors.forename: Sharon M
authors.initials: SM
authors.lastname: Homan
authors.forename: ChrisAnna M
authors.initials: CM
authors.lastname: Mink
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000907:Antibodies, Bacterial / Q000032:analysis; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D004311:Double-Blind Method; D005260:Female; D018073:Haemophilus Vaccines / Q000276:immunology*; D019741:Haemophilus influenzae type b / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009345:Neisseria meningitidis / Q000276:immunology; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D011446:Prospective Studies; D012449:Safety; D018074:Vaccines, Conjugate / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001425:Bacterial Outer Membrane Proteins; D018073:Haemophilus Vaccines; C061964:Haemophilus influenzae-type b polysaccharide-Neisseria meningitidis outer membrane protein conjugate vaccine; D011135:Polysaccharides, Bacterial; D018074:Vaccines, Conjugate