Immunogenicity of 2 serogroup B outer-membrane protein meningococcal vaccines: a randomized controlled trial in Chile.
BACKGROUND
Meningococcal disease occurs worldwide, and serogroup B disease accounts for a large proportion of cases. Although persons younger than 4 years are at greatest risk for serogroup B meningococcal disease, vaccine efficacy has not been demonstrated in this age group.


OBJECTIVE
To evaluate serum bactericidal activity (SBA) against homologous vaccine type strains and a heterologous Chilean epidemic strain of Neisseria meningitidis as a potential correlate for vaccine efficacy.


METHODS
Double-blind, randomized controlled trial conducted between March 14 and July 20, 1994. All blood samples were taken by December 1994.


METHODS
Santiago, Chile, where a clonal serogroup B meningococcal disease epidemic began in 1993.


METHODS
Infants younger than 1 year (n = 187), children aged 2 to 4 years (n = 183), and adults aged 17 to 30 years (n = 173).


METHODS
Participants received 3 doses of outer-membrane protein (OMP) meningococcal vaccine developed in either Cuba or Norway or a control vaccine, with each dose given 2 months apart. Blood samples were obtained at baseline, prior to dose 3, and at 4 to 6 weeks after dose 3.


METHODS
Immune response, defined as a 4-fold or greater rise in SBA titer 4 to 6 weeks after dose 3 compared with prevaccination titer.


RESULTS
Children and adult recipients of either meningococcal vaccine were more likely than controls to develop an immune response to the heterologous epidemic strain. After 3 doses of vaccine, 31% to 35% of children responded to the vaccine vs 5% to placebo; 37% to 60% of adults responded to vaccine vs 4% to placebo (P<.05 vs control for all). Infants, however, did not respond. In contrast, against homologous vaccine type strains, the response rate was 67% or higher among children and adults and 90% or higher among infants (P<.001 vs control for all). Subsequent SBA against 7 isogenic homologous target strains identified class 1 OMP as the immunodominant antigen.


CONCLUSIONS
These data suggest that neither serogroup B OMP meningococcal vaccine would confer protection during a heterologous epidemic. However, epidemic strain-specific vaccines homologous for class 1 OMP are promising candidates for the control of epidemic serogroup B meningococcal disease.
Tappero
J W
JW
Centers for Disease Control and Prevention, Meningitis and Special Pathogens Branch, Atlanta, GA 30333, USA. jwt0@cdc.gov
Lagos
R
R
Ballesteros
A M
AM
Plikaytis
B
B
Williams
D
D
Dykes
J
J
Gheesling
L L
LL
Carlone
G M
GM
Høiby
E A
EA
Holst
J
J
Nøkleby
H
H
Rosenqvist
E
E
Sierra
G
G
Campa
C
C
Sotolongo
F
F
Vega
J
J
Garcia
J
J
Herrera
P
P
Poolman
J T
JT
Perkins
B A
BA
D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000096:biosynthesis*; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines / Q000276:immunology*; D001770:Blood Bactericidal Activity; D002675:Child, Preschool; D002677:Chile; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D016056:Immunodominant Epitopes; D007223:Infant; D008297:Male; D008589:Meningococcal Infections / Q000517:prevention & control; D022401:Meningococcal Vaccines; D009345:Neisseria meningitidis / Q000145:classification* / Q000235:genetics / Q000276:immunology*; D012703:Serotyping
D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D016056:Immunodominant Epitopes; D022401:Meningococcal Vaccines