title: Double-blind study comparing the immunogenicity of a licensed DTwPHib-CRM197 conjugate vaccine (Quattvaxem) with three investigational, liquid formulations using lower doses of Hib-CRM197 conjugate.
abstract: We performed a double-blind clinical study to evaluate the safety and immunogenicity of four formulations of a DTwPHib full liquid vaccine, three of which contained fractional doses of the 10 microg-dose of CRM197-Hib conjugate vaccine. A total of 261 infants were enrolled and randomised to receive at 3, 4 and 5 months of age, in a double-blind fashion, one of the four DTwPHib vaccine formulations containing 10, 5, 2.5 or 1.25 microg of CRM197-Hib conjugate. Post-immunization reactions were similar in the four vaccine groups, they were mild, transient and resolved without sequelae. The seroconversion rates to anti-PRP titres > or = 0.15 microg/mL were 100%, 98%, 97% and 98% in the groups 10, 5, 2.5 and 1.25 microg, respectively. The seroconversion rates to anti-PRP titres > or =1 microg/mL were 95%, 97%, 88% and 90%, again respectively. Anti-PRP GMTs were 18, 17, 7.82 and 6.94 microg/mL, respectively. All subjects were protected against tetanus and diphtheria, and >80% seroconverted to pertussis. High, and similar, levels of anti-PRP GMTs were elicited by the formulations with 10 and 5 microg of CRM197-Hib conjugate. Although the formulations with 2.5 and 1.25 microg of CRM197-Hib elicited lower levels of anti-PRP GMTs, they were immunogenic and are possible candidates for further development.
authors.affiliation: Tartu University Children's Hospital, Outpatients Department, Oru Str. 3, 51014 Tartu, Estonia.
authors.forename: Eda
authors.initials: E
authors.lastname: Tamm
authors.forename: Alessandra
authors.initials: A
authors.lastname: Veronese
authors.forename: Mario
authors.initials: M
authors.lastname: Contorni
authors.forename: Sirli
authors.initials: S
authors.lastname: Meriste
authors.forename: Pantaleo
authors.initials: P
authors.lastname: Nacci
authors.forename: Simonetta
authors.initials: S
authors.lastname: Viviani
mesh_terms: D001426:Bacterial Proteins / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D002626:Chemistry, Pharmaceutical; D016001:Confidence Intervals; D004167:Diphtheria Toxin / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology; D015721:Diphtheria-Tetanus-Pertussis Vaccine / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D018073:Haemophilus Vaccines / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology*; D006801:Humans; D007115:Immunization Schedule; D007223:Infant; D035703:Therapies, Investigational / Q000379:methods*; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000009:adverse effects / Q000276:immunology
chemical_list: D001426:Bacterial Proteins; D004167:Diphtheria Toxin; D015721:Diphtheria-Tetanus-Pertussis Vaccine; D018073:Haemophilus Vaccines; D018074:Vaccines, Conjugate; C080881:diphtheria-tetanus-pertussis-haemophilus b conjugate vaccine; C028581:CRM197 (non-toxic variant of diphtheria toxin)