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.

Increased growth rate and amikacin resistance of Salmonella enteritidis after one‐month spaceflight on China’s Shenzhou‐11 spacecraft

“…Moreover, differentially expressed genes and proteins associated with phenotypic changes were observed in S. enteritidis . We found that the resistance to amikacin might be attributed to the downregulated gene oppA and oligopeptide transporter OppA, the role of which might be a rational target for novel antimicrobials and vaccines against pathogenic bacteria (Garmory & Titball, ; Ren et al, ). Although the potential for the development of novel antimicrobials that used the OppA system has yet to be realized, there is no doubt that this approach will have important significance in the future.…”

Ten-Year Study of the Stringently Defined Otitis-prone Child in Rochester, NY

“…16 Thus far, all 5 Mcat antigens evaluated showed a significant rise in serum IgG levels over time in healthy children from 6–30 months of age (p<0.001), with a rank order as follows: Msp22 = OppA > OMPCD = Hag = PilA2. We have recently commenced study of these antigens in sOP children.…”

“…18 We found significantly lower percentages of memory B cells in sOP children to 3 Spn protein antigens (PhtD, PhtE, and Ply) compared to NOP children Figure 5. 16 The percentage of circulating PhtD-specific memory B cells correlated with serum IgG levels to PhtD.…”

Stringently Defined Otitis Prone Children Demonstrate Deficient Naturally Induced Mucosal Antibody Response to Moraxella catarrhalis Proteins

“…Evaluating naturally induced humoral immune responses to Mcat proteins may disclose the immunogenicity of these antigens and functional activity of the antibodies elicited by these proteins in the targeted age and most vulnerable population, especially sOP children. We have found that during nasopharyngeal (NP) colonization by Mcat all four antigens, OMP CD, OppA, Hag, and PilA2, are immunogenic in both sOP and NOP children ( 16 ). The age-dependent increase of naturally induced serum antibody ranked as OppA > Hag5–9 > OMP CD > PilA2 in both sOP and NOP children (Ren et al, unpublished).…”