Understanding the immune responses to the meningococcal strain-specific vaccine MeNZB measured in studies of infants

Abstract

Vaccine trials with infants enrolled between 6 and 10 weeks of age (young infants) and 6 and 8 months of age (older infants) provided an opportunity to evaluate immunoglobulin G (IgG) isotype distribution and avidity maturation as indicators of antibody function and immunologic memory. Following vaccination with a strain-specific outer membrane vaccine, MeNZB, pre- and postvaccination sera were used to determine IgG isotype responses and avidity indices (AI) in subsets of vaccinated subjects. Measurements of IgG isotypes involved 100 infants from each trial. AI were measured in 50 infants from the young infant trial who received a fourth vaccine dose and in 40 older infants from whom serum was collected 7 months after the primary vaccination course. IgG1 and IgG3 dominated the responses to the vaccine. A modest linear correlation (P < 0.001) occurred between serum bactericidal antibody (SBAb) titers and the total IgG or the IgG1 antibody units in older infants. The young infants showed a modest linear correlation between SBAb and total IgG (P = 0.005) and a weak linear correlation between SBAb and IgG1 (P = 0.003). Increased avidity with age was demonstrated in both groups. The AI in the young infants increased from 51.5% (95% confidence interval [CI], 47.7 to 54.7) postvaccination to 68.7% (95% CI, 65.5 to 71.9%) following the fourth dose of vaccine (P < 0.001). The mean avidity of the older infants increased significantly (P = 0.00012) from 42.4% (95% CI, 39.1 to 45.3%) postvaccination to 50.4% (95% CI, 47.2 to 53.6%) 4 months later. A fourth dose of MeNZB is now being given to young infants at 10 months of age.

FIG. 1.

Isotype distribution for IgG1 and IgG3 in the two infant age groups: 6 to 10 weeks (n = 100) and 6 to 8 months (n = 100). IgG1, bars with diagonal lines; IgG3, shaded bars. Error bars represent standard errors of the means.

FIG. 2.

Comparison of the mean AI (solid line) and the mean total IgG (dashed line) measured in young infants (n = 50). The primary three-dose vaccination series started at age 6 to 10 weeks. For the post series, serum was collected after the primary vaccination series (post-3). Prebooster serum was collected prior to delivery of the fourth dose (pre-4). Postbooster serum was collected at 4 weeks postbooster (post-4).