Serum antibody response to Moraxella catarrhalis proteins OMP CD, OppA, Msp22, Hag, and PilA2 after nasopharyngeal colonization and acute otitis media in children

Abstract

Background: There is no licensed vaccine for Moraxella catarrhalis (Mcat), which is a prominent bacterium causing acute otitis media (AOM) in children and lower respiratory tract infections in adults. Nasopharyngeal (NP) colonization caused by respiratory bacteria results in natural immunization of the host. To identify Mcat antigens as vaccine candidates, we evaluated the development of naturally induced antibodies to 5 Mcat surface proteins in children 6-30 months of age during Mcat NP colonization and AOM.

Methods: Human serum IgG against the recombinant Mcat proteins, outer membrane protein (OMP) CD, oligopeptide permease (Opp)A, hemagglutinin (Hag), Moraxella surface protein (Msp)22, and PilA clade 2 (PilA2) was quantitated by using an ELISA assay.

Results: There were 223 Mcat NP colonization episodes documented in 111 (60%) of 184 children in the study. Thirty five Mcat AOM episodes occurred in 30 (16%) of 184 children. All 5 Mcat candidate vaccine antigens evaluated stimulated a significant rise in serum IgG levles over time from 6 to 36 months of age (P<0.001), with a rank order as follows: Msp22=OppA>OMP CD=Hag=PilA2. Children with no detectable Mcat NP colonization showed a higher serum IgG level against OppA, Hag, and Msp22 compared to those with Mcat NP colonization (P<0.05). Individual data showed that some children responded to AOM with an antibody increase to one or more of the studied Mcat proteins but some children failed to respond.

Conclusions: Serum antibody to Mcat candidate vaccine proteins OMP CD, OppA, Msp22, Hag, and PilA2 increased with age in naturally immunized children age 6-30 months following Mcat NP colonization and AOM. High antibody levels against OppA, Msp22, and Hag correlated with reduced carriage. The results support further investigation of these vaccine candidates in protecting against Mcat colonization and infection.

Keywords: Acute otitis media; Antigen; Carriage; Immunogenicity; Nasopharyngeal colonization; Natural immunization; Recombinant proteins; Vaccine.

Fig. 1

Serum IgG antibody levels to Mcat proteins OMP CD, OppA, Msp22NL, Hag5–9, and PilA2 in healthy children increased with age. Plots of the geometric mean concentrations (ng/ml) with the 95% confidence interval during 7 sampling visits at 6, 9, 12, 15, 18, 24, 30 mo of age. The y-axis is presented as log2 scale. The numbers of sera included at each time point were 56, 67, 76, 75, 71, 73, 58, respectively.

Fig. 2

Comparison of serum IgG antibody concentration (ng/ml) to Mcat proteins OMP CD (A), OppA (B), Msp22NL (C), Hag5–9 (D), and PilA2 (E) in Mcat NP colonized (broken line) and non-colonized (solid line) healthy children from 6 to 30 mo of age. Serum anti-Mcat protein specific IgG antibody concentrations were determined with a quantitative ELISA and then power transformed using the Box–Cox method. The numbers of sera included at each time point were 27, 30, 39, 36, 33, 31, 27 for Mcat-colonized children and 29, 37, 37, 39, 38, 42, 31 for non-colonized children. Linear models including transformed antibody concentrations as response, age number and colonization indicator as predictors were used for comparison between colonized and non-colonized groups. Age numbers were log-transformed and nonlinear relationships were captured by including a quadratic age term. In order to control for subject-level dependence induced by repeated measures, a bootstrap procedure was used to estimate statistical significance, using subject-level resampling. The P-values correspond to the regression coefficient (beta not equal to 0) associated with the group factor (group main effect). P < 0.05 was considered significant.

Fig. 3

Individual serum IgG antibody levels (ng/ml) to Mcat proteins OMP CD (A, n = 34), OppA (B, n = 34), Msp22NL (C, n = 34), Hag5–9 (D, n = 32), and PilA2 (E, n = 35) in acute and convalescent sera of children with Mcat AOM.