title: Effect of aluminum adjuvants on safety and immunogenicity of Haemophilus influenzae type b-CRM197 conjugate vaccine.
abstract: OBJECTIVE
  The present study was carried out to evaluate the safety and immunogenicity of the Haemophilus influenzae type b-CRM197 (Hib-CRM197) conjugate vaccine in relation to the change of adjuvant from aluminum hydroxide to aluminum phosphate (AlPO4).
  
  
  METHODS
  The present study was a clinical phase II, observer-blind, randomized, multicenter, controlled study. Subjects were healthy infants aged 6-12 weeks, eligible for expanded program of immunization (EPI) routine vaccination and admitted to Hacettepe University Department of Social Pediatrics and Gülveren Health Center, Ankara. A total of 520 healthy infants were randomized in a 2:2:1 ratio to receive at either Chiron Hib/AlPO4 vaccine or VaxemHib (aluminum hydroxide adjuvant) vaccine or HibTiter (no adjuvant). Vaccines were administered simultaneously with routine diphtheria, tetanus and pertussis (DTaP) and oral polio vaccine (OPV) vaccines at 2, 4 and 6 months of age. Blood samples for anti-plain polysaccharide (PRP) antibody measurement were collected before the first vaccination and 1 month after the last vaccination. After each vaccination parents filled out a diary for 7 days.
  
  
  RESULTS
  Out of 520 subjects enrolled, 514 received three doses and were included for safety analysis. Local and systemic reactions occurred with low and similar frequencies in all groups. Only erythema was more common in Chiron Hib/AlPO4 vaccine (19, 10, 11% in Chiron Hib/AlPO4, VaxemHib and HibTiter, respectively, P < 0.05). Nine serious adverse events were reported in seven cases of which none were related to vaccines. A total of 504 subjects were included in the immunogenicity analysis. The three vaccines were highly immunogenic and equivalent in terms of percentage of acquisition of long-term protective levels. The anti-PRP geometric mean titers were 9.9, 8.3 and 5.14 micro g/mL, respectively (P < 0.05).
  
  
  CONCLUSIONS
  The use of aluminum compounds adjuvants in Hib-CRM197 conjugate vaccines does not impact the safety profile, while it does increase the magnitude of anti-PRP antibody titers.
authors.affiliation: Departments of Paediatric Infectious Diseases and Social Pediatrics Medical Faculty, Hacettepe University, Ankara, Turkey.
authors.forename: Güler
authors.initials: G
authors.lastname: Kanra
authors.forename: Simonetta
authors.initials: S
authors.lastname: Viviani
authors.forename: Kadriye
authors.initials: K
authors.lastname: Yurdakök
authors.forename: Elif
authors.initials: E
authors.lastname: Ozmert
authors.forename: Alessandra
authors.initials: A
authors.lastname: Anemona
authors.forename: Songül
authors.initials: S
authors.lastname: Yalçin
authors.forename: Okan
authors.initials: O
authors.lastname: Demiralp
authors.forename: Nihan
authors.initials: N
authors.lastname: Bilgili
authors.forename: Ates
authors.initials: A
authors.lastname: Kara
authors.forename: Ali Bülent
authors.initials: AB
authors.lastname: Cengiz
authors.forename: Belgin
authors.initials: B
authors.lastname: Mutlu
authors.forename: Alexandra
authors.initials: A
authors.lastname: Baldini
authors.forename: Elisa
authors.initials: E
authors.lastname: Marchetti
authors.forename: Audino
authors.initials: A
authors.lastname: Podda
mesh_terms: D000276:Adjuvants, Immunologic / Q000009:adverse effects / Q000494:pharmacology*; D017607:Aluminum Compounds / Q000009:adverse effects / Q000494:pharmacology*; D000536:Aluminum Hydroxide / Q000009:adverse effects / Q000494:pharmacology; D000917:Antibody Formation; D001426:Bacterial Proteins / Q000009:adverse effects / Q000276:immunology*; D004311:Double-Blind Method; D018073:Haemophilus Vaccines / Q000009:adverse effects / Q000276:immunology*; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007223:Infant; D010710:Phosphates / Q000009:adverse effects / Q000494:pharmacology*; D011135:Polysaccharides, Bacterial / Q000276:immunology; D018074:Vaccines, Conjugate / Q000276:immunology
chemical_list: D000276:Adjuvants, Immunologic; D017607:Aluminum Compounds; D001426:Bacterial Proteins; D018073:Haemophilus Vaccines; D007074:Immunoglobulin G; D010710:Phosphates; D011135:Polysaccharides, Bacterial; D018074:Vaccines, Conjugate; C061963:HibTITER protein, Haemophilus influenzae; D000536:Aluminum Hydroxide; C012714:aluminum phosphate