title: Safety and immunogenicity of Haemophilus influenzae type B vaccine given in combination with DTwP at 6, 10 and 14 weeks of age.
abstract: OBJECTIVE
  To assess the immunogenicity and reactogenicity of a tetanus conjugate Haemophilus influenzae type b vaccine (Act-Hib) when extemporaneously mixed and administered as a DTwP-Hib combination using an Indian DTwP vaccine (BE DTwP) in comparison with a licensed DTwP-Hib combination vaccine.
  
  
  METHODS
  378 healthy infants were enrolled and randomly allocated to receive either three doses, at 6, 10 and 14 weeks of age, of Act-Hib in combination with BE DTwP (Group A, n = 160), TetrAct-Hib (Group B, n = 160), or BE DTwP and Act-Hib as separate injections (Group C, n = 58). Sera collected before the first dose and one month after the third dose were tested for antibodies to vaccine antigens. Safety was determined using parental diary cards.
  
  
  RESULTS
  Anti-Hib antibody concentrations indicative of short-term protection (> 0.15 g/ml) were elicited in all but one subject in Group A (99.3%), and all subjects in Groups B and C. The concentration of 1 g/ml, considered to provide long-term protection, was achieved in 96.7%, 100% and 98.2% of the infants in Groups A, B and C, respectively. All children displayed satisfactory responses to the three DTwP component antigens, TetrAct-Hib eliciting higher titers against diphtheria and tetanus than BE DTwP. No vaccine-associated serious adverse events occurred. The BE DTwP vaccine was associated with more reports of fever than TetrAct-Hib, but most symptoms were regarded as mild and all resolved without sequelae.
  
  
  CONCLUSIONS
  Combining Act-Hib and a local DTwP vaccine did not affect the anti-Hib response. In countries where DTwP vaccine available for use in the EPI program is manufactured by a local or other developing country manufacturer, mixing it with lyophilised Act-Hib is a reasonable option though the immunogenicity may have to be documented before routine use. However, use of TetrAct-Hib combination vaccine would be preferable in view of its lower reactogenicity and superior immunogenicity with respect to diphtheria and tetanus.
authors.affiliation: Department of Child Health, Christian Medical College and Hospital, Vellore, Tamil Nadu, India. cheri@cmcvellore.ac.in
authors.forename: Thomas
authors.initials: T
authors.lastname: Cherian
authors.forename: Niranjan
authors.initials: N
authors.lastname: Thomas
authors.forename: P
authors.initials: P
authors.lastname: Raghupathy
authors.forename: Isabelle
authors.initials: I
authors.lastname: Durot
authors.forename: Anil
authors.initials: A
authors.lastname: Dutta
mesh_terms: D004168:Diphtheria Toxoid / Q000009:adverse effects* / Q000276:immunology* / Q000627:therapeutic use; D005260:Female; D006192:Haemophilus Infections / Q000517:prevention & control*; D018073:Haemophilus Vaccines / Q000009:adverse effects* / Q000276:immunology* / Q000627:therapeutic use; D019741:Haemophilus influenzae type b / Q000276:immunology*; D006801:Humans; D007115:Immunization Schedule; D007194:India; D007223:Infant; D008297:Male; D013745:Tetanus Toxoid / Q000009:adverse effects* / Q000276:immunology* / Q000627:therapeutic use; D017778:Vaccines, Combined / Q000009:adverse effects / Q000276:immunology; D018074:Vaccines, Conjugate
chemical_list: D004168:Diphtheria Toxoid; D018073:Haemophilus Vaccines; C055753:Haemophilus influenza type b polysaccharide vaccine-tetanus toxin conjugate; C052180:Haemophilus influenzae type b-polysaccharide vaccine-diphtheria toxoid conjugate; D013745:Tetanus Toxoid; D017778:Vaccines, Combined; D018074:Vaccines, Conjugate