Immunogenicity and safety of an investigational combined haemophilus influenzae type B-Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine.

Author(s): Nolan T, Richmond P, Marshall H, McVernon J, Alexander K, Mesaros N, Aris E, Miller J, Poolman J, Boutriau D

Affiliation(s): Vaccine and Immunisation Research Group, Murdoch Children's Research Institute and School of Population Health, University of Melbourne, Victoria, Australia. t.nolan@unimelb.edu.au

Publication date & source: 2011-03, Pediatr Infect Dis J., 30(3):190-6.

Publication type: Comparative Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't

BACKGROUND: Neisseria meningitidis serogroups B, C, and Y cause most meningococcal disease in industrialized countries. A Haemophilus influenzae type b-meningococcal serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY-TT) was evaluated. METHODS: A total of 1104 infants (randomized 3:1:1) were vaccinated at 2, 4, and 6 months with HibMenCY-TT, MenC-CRM197 + Hib-TT, or Hib-TT. At 12 to 15 months, HibMenCY-TT and MenC-CRM-primed children received HibMenCY-TT; Hib-TT-primed received N. meningitidis serogroup B Hib-outer membrane protein complex. Antibody concentrations and rabbit/human complement serum bactericidal antibody titers (rSBA/hSBA) were determined. Safety was monitored after each dose (diary cards for first 31 days) until 6 months postdose 4. RESULTS: Postdose 3, rates of antipolyribosylribitol phosphate >/= 1 mug/mL and rSBA-MenC >/=1:128 in HibMenCY-TT recipients were noninferior to licensed controls. Percentages reaching 0.15 mug/mL (1.0 mug/mL postdose 3) and antipolyribosylribitol phosphate GMC were significantly higher after HibMenCY-TT than Hib-TT postdose 2 and postdose 3. The GMC remained significantly higher before and after dose 4. Proportions of HibMenCY-TT recipients with rSBA >/= 1:8 were 95.6% (MenC), 98.6% (MenY) postdose-2, >/= 99% for MenC/Y postdose 3 and 4; hSBA >/= 1:4 were 95.5% (MenC), 89.8% (MenY) postdose 2, >97% for MenC/Y postdose 3 and 4. HibMenCY-TT had a similar safety profile to control vaccines. CONCLUSIONS: HibMenCY-TT induced noninferior Hib and MenC responses compared with monovalent Hib and MenC conjugates with a comparable safety profile. Bactericidal antibodies against MenC/Y were induced after 2 doses of HibMenCY-TT.