Immunogenicity and safety of an investigational combined haemophilus influenzae type B-Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine.
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 μg/mL and rSBA-MenC ≥1:128 in HibMenCY-TT recipients were noninferior to licensed controls. Percentages reaching 0.15 μg/mL (1.0 μg/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.
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
Terry
T
Nolan
Peter
P
Richmond
Helen
H
Marshall
Jodie
J
McVernon
Karyn
K
Alexander
Narcisa
N
Mesaros
Emmanuel
E
Aris
Jacqueline
J
Miller
Jan
J
Poolman
Dominique
D
Boutriau
D000907:Antibodies, Bacterial / Q000097:blood; D001770:Blood Bactericidal Activity; D018073:Haemophilus Vaccines / Q000009:adverse effects* / Q000276:immunology*; D006801:Humans; D007117:Immunization, Secondary / Q000379:methods; D007223:Infant; D058248:Serum Bactericidal Antibody Assay; D013745:Tetanus Toxoid / Q000009:adverse effects* / Q000276:immunology*; D014611:Vaccination / Q000379:methods; D018074:Vaccines, Conjugate / Q000009:adverse effects / Q000276:immunology
D000907:Antibodies, Bacterial; D018073:Haemophilus Vaccines; C527605:Hib-MenCY-TT vaccine; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate