Protective activity of group C anticapsular antibodies elicited in two-year-olds by an investigational quadrivalent Neisseria meningitidis-diphtheria toxoid conjugate vaccine.
BACKGROUND
Quadrivalent capsular group A, C, Y and W-135 meningococcal conjugate (MC-4) vaccines are under development


OBJECTIVE
Predict efficacy of an investigational MC-4 vaccine in 2-year-old children for prevention of group C disease.


METHODS
Measurement of group C antibody concentrations, avidity and bactericidal and passive protective activity in sera from 2-year-olds given 1 dose of MC-4 vaccine (N = 30) and 3-year-olds (N = 30) and adults (N = 26) given 1 dose of meningococcal polysaccharide (MPS-4) vaccine.


RESULTS
One month after vaccination, the geometric mean anticapsular antibody concentration of children given MC-4 vaccine (3.1 microg/ml) was lower than that of control children (5.1 microg/ml; P < 0.04) or adults immunized with MPS-4 vaccine (22.9 microg/ml; P < 0.001). However, the percent of sera with protective bactericidal titers of >/=1/4 was higher in children given MC-4 vaccine (50%, versus 17% in children given MPS-4 vaccine; P < 0.02) and was not significantly different from that of immunized adults (65%). In children, the mean antibody avidity at 1 month was higher in the MC-4 group (22 nM versus 16 nM in the MPS-4 group; P = 0.002), and at 6 months increased in the MC-4 group (28 nM; P < 0.001), but not in the MPS-4 vaccine group (17 nM). Higher avidity antibody gave greater passive protection in the infant rat bacteremia model than did lower avidity antibody (P < 0.03).


CONCLUSIONS
Although MPS-4 vaccine elicited higher group C serum antibody concentrations in 3-year-olds than did MC-4 vaccine in 2-year-olds, the higher antibody avidity after MC-4 vaccine resulted in higher bactericidal and passive protective activity.
Granoff
Dan M
DM
Children's Hospital Oakland Research Institute, Oakland, CA, USA. dgranoff@chori.org
Harris
Shannon L
SL
D000704:Analysis of Variance; D000907:Antibodies, Bacterial / Q000032:analysis*; D016667:Bacterial Capsules / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D004168:Diphtheria Toxoid / Q000008:administration & dosage*; D015507:Drugs, Investigational; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007111:Immunity, Cellular / Q000502:physiology; D007115:Immunization Schedule; D008297:Male; D008589:Meningococcal Infections / Q000097:blood / Q000276:immunology* / Q000517:prevention & control; D022401:Meningococcal Vaccines / Q000008:administration & dosage*; D038542:Neisseria meningitidis, Serogroup C / Q000276:immunology*; D011336:Probability; D018570:Risk Assessment; D018709:Statistics, Nonparametric; D018074:Vaccines, Conjugate / Q000008:administration & dosage
D000907:Antibodies, Bacterial; D004168:Diphtheria Toxoid; D015507:Drugs, Investigational; D022401:Meningococcal Vaccines; D018074:Vaccines, Conjugate