Antibody avidity and immunoglobulin G isotype distribution following immunization with a monovalent meningococcal B outer membrane vesicle vaccine

Abstract

The avidity maturation and immunoglobulin G (IgG) isotype distribution of antibodies after vaccination with a meningococcal B outer membrane vesicle (OMV) vaccine were evaluated as indicators of protective immunity. Pre- and postvaccination sera from 134 healthy toddlers (ages, 2 to 3 years) immunized with a monovalent meningococcal B OMV (serosubtype P1.7-2,4) vaccine adsorbed with AlPO(4) or Al(OH)(3) were analyzed by enzyme-linked immunosorbent assay (ELISA) methods. The children were vaccinated three times with intervals of 3 to 6 weeks between vaccinations or twice with an interval of 6 to 10 weeks between vaccinations. A booster was given after 20 to 40 weeks. The avidity index (AI) of antibodies increased significantly during the primary series of vaccinations and after the booster was given. No differences in AIs were found when the results obtained with the two vaccination schedules or with the two adjuvants were compared. After vaccination, IgG1 was the predominant IgG isotype, followed by IgG3. No IgG2 or IgG4 was detected. There was a strong correlation between serum bactericidal activity (SBA) and ELISA titers (r = 0.85 [P < 0.0001] for total IgG, r = 0.83 for IgG1 [P < 0.0001], r = 0.82 for IgG3 [P < 0.0001], and r = 0.84 [P < 0.0001] for the avidity titer). When two subgroups with similar anti-OMV IgG levels were compared before and after the booster vaccination, the higher AI after the booster vaccination was associated with significantly increased SBA. We concluded that avidity maturation occurs after vaccination with a monovalent meningococcal B OMV vaccine, especially after boosting, as indicated by a significant increase in the AI. Vaccination with the monovalent OMV vaccine induced mainly IgG1 and IgG3 isotypes, which are considered to be most important for protection against meningococcal disease. An increase in the AI of antibodies is associated with increased SBA, independent of the level of specific IgG and the IgG isotype distribution. Measuring the AI and IgG isotype distribution of antibodies after vaccination can be a supplementary method for predicting protective immunity for evaluation in future phase III trials with meningococcal serogroup B vaccines.

FIG. 1.

Mean AI (⧫), mean level of total IgG against P1.7-2,4 OMVs (▪), and mean level of anti-OMV IgG against PorA-negative OMVs (▴) in sera of 134 toddlers after immunization with a monovalent meningococcal B OMV vaccine. The error bars indicate 95% CIs. prim., primary.

FIG. 2.

Mean AI for each group. The four kinds of bars show the mean AIs obtained with the two different vaccine adjuvants and the two different vaccination schedules. Open bars and solid bars, two primary vaccinations followed by a booster vaccination (2+1 schedule) with Al(OH)₃ and AlPO₄, respectively; mesh bars and dotted bars, three primary vaccinations followed by a booster vaccination (3+1 schedule) with Al(OH)₃ and AlPO₄, respectively. The error bars indicate 95% CIs.

FIG. 3.

Serum log₁₀ IgG isotype concentrations against P1.7-2,4 OMVs for each group. No IgG2 or IgG4 was found. 2+1, two primary vaccinations followed by a booster vaccination; 3+1, three primary vaccinations followed by a booster vaccination. Open bars, IgG1; solid bars, IgG3. The error bars indicate 95% CIs.

FIG. 4.

Scatter plots of log₁₀ SBA titer versus AI (A) (r = 0.36), log₁₀ avidity titer (B) (r = 0.84), and log₁₀ total IgG titer (C) (r = 0.85).