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

• Published in: Vaccine Vol. 23; no. 14; pp. 1715 - 1719
• Main Authors: Tamm, Eda, Veronese, Alessandra, Contorni, Mario, Meriste, Sirli, Nacci, Pantaleo, Viviani, Simonetta
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 25.02.2005; Elsevier; Elsevier Limited
• Subjects: Antigens; Applied microbiology; Bacterial Proteins - administration & dosage; Bacterial Proteins - adverse effects; Bacterial Proteins - immunology; Biological and medical sciences; Chemistry, Pharmaceutical; Combined vaccines; Confidence Intervals; Diphtheria; Diphtheria Toxin - administration & dosage; Diphtheria Toxin - adverse effects; Diphtheria Toxin - immunology; Diphtheria-Tetanus-Pertussis Vaccine - administration & dosage; Diphtheria-Tetanus-Pertussis Vaccine - adverse effects; Diphtheria-Tetanus-Pertussis Vaccine - immunology; Dose-Response Relationship, Immunologic; Double-Blind Method; DTwPHib full liquid vaccine; Fractional doses Hib vaccine; Fundamental and applied biological sciences. Psychology; Haemophilus Vaccines - administration & dosage; Haemophilus Vaccines - adverse effects; Haemophilus Vaccines - immunology; Humans; Immunization; Immunization Schedule; Immunogenicity; Infant; Licenses; Microbiology; Mortality; Parents & parenting; Tetanus; Therapies, Investigational - methods; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Vaccines, Conjugate - administration & dosage; Vaccines, Conjugate - adverse effects; Vaccines, Conjugate - immunology; Italy; DTwPHib full liquid vaccine; Combined vaccines; Fractional doses Hib vaccine; Mixed vaccine; Immunogenicity
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2004.09.028

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 μg-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 μg 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 ≥ 0.15 μg/mL were 100%, 98%, 97% and 98% in the groups 10, 5, 2.5 and 1.25 μg, respectively. The seroconversion rates to anti-PRP titres ≥1 μg/mL were 95%, 97%, 88% and 90%, again respectively. Anti-PRP GMTs were 18, 17, 7.82 and 6.94 μg/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 μg of CRM197-Hib conjugate. Although the formulations with 2.5 and 1.25 μg of CRM197-Hib elicited lower levels of anti-PRP GMTs, they were immunogenic and are possible candidates for further development.