Induction of immunologic memory by conjugated vs plain meningococcal C polysaccharide vaccine in toddlers: a randomized controlled trial.
BACKGROUND
Meningococcal polysaccharide vaccines are not used routinely in infants and toddlers, the groups at highest risk of invasive disease, because of poor immunologic responses to the Neisseria meningitidis serogroup C polysaccharide in these age groups. Meningococcal C conjugate vaccines offer the prospect of circumventing this problem.


OBJECTIVE
To assess the immunogenicity and the induction of immunologic memory in toddlers by meningococcal C conjugate vaccine.


METHODS
A multicenter, randomized, observer-blinded controlled trial.


METHODS
Urban and suburban family medicine or pediatric practices.


METHODS
Two hundred eleven healthy toddlers aged 15 to 23 months.


METHODS
Two injections at 2 months apart of meningococcal C conjugate (group 1, n = 69), plain meningococcal polysaccharide (group 2, n = 72), or hepatitis B virus vaccine (group 3, n = 70). All toddlers received a follow-up dose of plain meningococcal polysaccharide vaccine 12 months later.


METHODS
IgG meningococcal C anticapsular antibody concentrations determined by enzyme-linked immunosorbent assay and complement-mediated bactericidal antibody.


RESULTS
In group 1, the magnitude of the IgG response to meningococcal C conjugate vaccine was more than 4-fold higher after dose 1 and more than 10-fold higher after dose 2 compared with meningococcal polysaccharide vaccine (group 2) (P<.001). Higher titers persisted in the meningococcal C conjugate group for at least 12 months (P<.001). Group 1, primed with meningococcal C conjugate, had 25-fold higher IgG responses to the meningococcal polysaccharide 1-year booster dose than the controls who had received hepatitis B virus vaccine initially and were given meningococcal polysaccharide vaccine 1 year later for the first time (P<.001). In contrast, group 2, primed with meningococcal polysaccharide, had a 2-fold lower response to the 1-year booster meningococcal polysaccharide dose than the hepatitis B virus control group (P = .006). Serum bactericidal responses paralleled the enzyme-linked immunosorbent assay responses.


CONCLUSIONS
Immunization of toddlers with meningococcal C conjugate vaccine induces high titers of anticapsular and bactericidal antibody. Furthermore, this vaccine induces immunologic memory to meningococcal C polysaccharide. In contrast, meningococcal polysaccharide vaccine is less immunogenic than the conjugate vaccine and also induces a hyporesponsive state that persists for at least 12 months.
MacDonald
N E
NE
University of Ottawa, Ontario, Canada. macdonaldvn@cheo.on.ca
Halperin
S A
SA
Law
B J
BJ
Forrest
B
B
Danzig
L E
LE
Granoff
D M
DM
D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D017325:Hepatitis B Vaccines / Q000276:immunology; D006801:Humans; D007117:Immunization, Secondary; D007074:Immunoglobulin G / Q000032:analysis / Q000276:immunology*; D007156:Immunologic Memory; D007223:Infant; D008589:Meningococcal Infections / Q000517:prevention & control*; D009345:Neisseria meningitidis / Q000145:classification / Q000276:immunology*; D011135:Polysaccharides, Bacterial / Q000276:immunology*; D012703:Serotyping; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000008:administration & dosage / Q000276:immunology*
D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D017325:Hepatitis B Vaccines; D007074:Immunoglobulin G; D011135:Polysaccharides, Bacterial; D018074:Vaccines, Conjugate