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Protective Activity of Group C Anticapsular Antibodies Elicited in Two-Year-Olds by an Investigational Quadrivalent Neisseria meningitidis-Diphtheria Toxoid Conjugate Vaccine

Granoff, Dan M. MD; Harris, Shannon L. PhD

The Pediatric Infectious Disease Journal: June 2004 - Volume 23 - Issue 6 - p 490-497
doi: 10.1097/01.inf.0000129686.12470.e6
Original Studies

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.

Design: 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 μg/ml) was lower than that of control children (5.1 μg/ml; P < 0.04) or adults immunized with MPS-4 vaccine (22.9 μg/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−1 versus 16 nM−1 in the MPS-4 group; P = 0.002), and at 6 months increased in the MC-4 group (28 nM−1; P < 0.001), but not in the MPS-4 vaccine group (17 nM−1). 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.

From the Children’s Hospital Oakland Research Institute, Oakland, CA.

Supported in part by grants RO1 AI 45642 and AI46464 from the National Institutes of Allergy and Infectious Disease, National Institutes of Health, and by a grant from Aventis Pasteur.

The vaccine trial in adults was performed in the Pediatric Clinical Research Center of Children’s Hospital and Research Center at Oakland and was supported by grant M01-RR01271 from National Center for Research Resources, National Institutes of Health.

Accepted for publication January 30, 2004.

Address for reprints: Dan M. Granoff, MD, 5700 Martin Luther King Jr. Way, Oakland, CA 94609. Fax 510-450-7915; E-mail dgranoff@chori.org

© 2004 Lippincott Williams & Wilkins, Inc.