Abstract

Background: Meningococcal C conjugate (Men C) vaccines have been routinely used in the UK since November, 1999. Little information exists regarding antibody persistence or immunologic memory after infant vaccination or response to a first dose at 4 years.
Methods: Ninety-five children immunized at 2, 3 and 4 months of age with 0 or 3 doses of Men C vaccine, boosted with Men C or meningococcal A/C polysaccharide vaccine at 12 months, received a single dose of Men C vaccine at 4 years; 103 age-matched controls were recruited. Pre- and postvaccination Men C IgG (enzyme-linked immunosorbent assay) antibody titers and serum bactericidal activity (SBA) were measured. Safety data were also collected.
Results: Baseline SBA titers of >/=1/4 were observed in 87% of children after at least 3 doses of Men C vaccine in infancy compared with 21% of controls. Reciprocals of postvaccination SBA geometric mean titers in those with four prior doses [3803 (95% confidence interval 3489, 4146)] were significantly higher than controls [33 (95% confidence interval 20, 55)] (P < 0.001). Memory was attenuated by the 12-month meningococcal A/C polysaccharide booster [734 (95% confidence interval 484, 1115)] (P < 0.001). All children had IgG responses to a first dose of Men C vaccine, 80% achieving SBA titers of >/=1/4 (77% >/=1/8). The vaccine was safe and well-tolerated.
Conclusion: Infant immunization with Men C produced persistent antibody and immunologic memory at 4 years. All children made IgG antibodies after a first dose at this age, with 80% showing bactericidal activity. Clarification of the best measures of Men C vaccine-induced protection is needed, through correlation of immunogenicity data such as this with UK vaccine efficacy estimates.

Introduction

Conjugate vaccines against meningococcus serogroup C (Men C) were introduced as part of the United Kingdom's routine infant immunization schedule in November, 1999, as an accelerated primary course at 2, 3 and 4 months of age without a booster in the second year of life. In a concurrent "catch up" campaign, infants age 6 to 12 months were offered two doses of vaccine, and those 12 months to 18 years of age were offered a single dose. Men C conjugate vaccines are safe and immunogenic, and they prime for immunologic memory after three doses in infancy.^[1-3] Little information exists regarding the responses of preschool age children after a first dose of this vaccine. Data are also lacking regarding the duration of vaccine attributable protection induced by Men C conjugates in infancy.

In this study measures of Men C-specific IgG [enzyme-linked immunosorbent assay (ELISA)] antibodies and serum bactericidal activity (SBA) have been applied to antibody persistence and booster responses to immunization in a cohort of preschool age children who received various doses of Men C conjugate vaccine in infancy. A comparison group of age-matched children was also studied, allowing an assessment of the occurrence of natural immunity in preschoolers and their responses to a first dose of vaccine. Controls were subdivided into two groups for a comparison of two lots of vaccine. The safety profile of the vaccine in this age group was also evaluated.