title: Safety and immunogenicity of two Haemophilus influenzae type b polysaccharide-tetanus toxoid conjugate vaccines (PRP-T) given with diphtheria-tetanus-pertussis vaccine to young Papua New Guinean children.
abstract: BACKGROUND
  In view of high mortality and morbidity from Haemophilus influenzae type b (Hib) in young Papua New Guinean children, the incorporation of a Hib conjugate vaccine into a nationwide immunization program would be of major public health benefit.
  
  
  METHODS
  We evaluated the safety and immunogenicity of a lyophilized and a liquid form of Hib polysaccharide-tetanus toxoid conjugate vaccines (PRP-T) given in the same syringe as diphtheria-tetanus-pertussis (DTP) vaccine to children in Goroka, Eastern Highlands Province. In Part 1 of the study 209 children were randomized to receive at ages 1, 2 and 3 months either DTP alone or a liquid formulation of DTP/PRP-T or lyophilized PRP-T dissolved in DTP suspension. A further 75 children were given the liquid DTP/PRP-T formulation at ages 2, 3 and 4 months (Part 2). 54 children aged 15-18 months were given a booster of the same preparation of PRP-T/DTP as they had received during Part 1. Blood for antibody assays was collected at enrolment, before (Part 1 only) and one month after the third dose, then just before and 3 weeks after the booster dose.
  
  
  RESULTS
  Follow-up to age of 12 months showed that PRP-T was safe with no evidence of impaired response to individual vaccine components when combined with DTP. Geometric mean titres (GMTs) of anti-PRP antibody before vaccination (n = 64, mean age 41 days), after 2 doses (mean age 99 days) and after 3 doses (mean age 132 days) of the lyophilized formulation were 0.21, 1.48 and 5.04 microg/ml, respectively, with 58% and 89% having anti-PRP antibody titres > or = 1.0 microg/ml after 2 and 3 doses, respectively. Anti-PRP antibody responses to the liquid Hib vaccine formulation were lower (GMT post-dose 3 = 0.48 microg/ml) than to the lyophilized formulation, but better responses were elicited from older children (Part 2; GMT post-dose 3 = 0.78 microg/ml, with 79% > or = 0.15 microg/ml). Both PRP-T preparations elicited excellent booster responses suggesting that children are likely to be protected if exposed to Hib infection.
  
  
  CONCLUSIONS
  Lyophilized PRP-T given together with DTP is safe and immunogenic when given to young infants. The liquid DTP/PRP-T formulation showed a lower immunogenicity than in earlier studies with this vaccine, which might have been due to exposure to low temperature during shipment or the younger age at immunization.
authors.affiliation: Papua New Guinea Institute of Medical Research, Goroka.
authors.forename: D
authors.initials: D
authors.lastname: Lehmann
authors.forename: M
authors.initials: M
authors.lastname: Kakazo
authors.forename: G
authors.initials: G
authors.lastname: Saleu
authors.forename: J
authors.initials: J
authors.lastname: Taime
authors.forename: A
authors.initials: A
authors.lastname: Javati
authors.forename: P
authors.initials: P
authors.lastname: Namuigi
authors.forename: M P
authors.initials: MP
authors.lastname: Alpers
authors.forename: B
authors.initials: B
authors.lastname: Wegmüller
authors.forename: M
authors.initials: M
authors.lastname: Zellmeyer
authors.forename: E
authors.initials: E
authors.lastname: Fürer
authors.forename: J U
authors.initials: JU
authors.lastname: Que
authors.forename: C
authors.initials: C
authors.lastname: Herzog
mesh_terms: D000284:Administration, Oral; D000704:Analysis of Variance; D016009:Chi-Square Distribution; D002675:Child, Preschool; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006192:Haemophilus Infections / Q000276:immunology* / Q000517:prevention & control*; D018073:Haemophilus Vaccines / Q000008:administration & dosage*; D006801:Humans; D007109:Immunity / Q000502:physiology; D007115:Immunization Schedule; D007117:Immunization, Secondary / Q000379:methods; D007223:Infant; D007231:Infant, Newborn; D007273:Injections, Intramuscular; D008297:Male; D010219:Papua New Guinea; D012449:Safety; D012680:Sensitivity and Specificity; D013745:Tetanus Toxoid / Q000008:administration & dosage*; D014611:Vaccination / Q000379:methods*
chemical_list: D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; C055753:Haemophilus influenza type b polysaccharide vaccine-tetanus toxin conjugate; D013745:Tetanus Toxoid