Analysis of Human Serum Immunoglobulin G againstO-Acetyl-Positive andO-Acetyl-Negative Serogroup W135 Meningococcal Capsular Polysaccharide

Abstract

The capsular polysaccharide of Neisseria meningitidis serogroup W135 is expressed in both O-acetyl-positive (OA ؉ ) and O-acetyl-negative (OA ؊ ) forms. This study investigates the impact of OA status (OA ؉ versus OA ؊ ) on serological measurements of anti-W135 immunoglobulin G (IgG) antibodies in immunized adults. W135-specific serum antibody assignments were made for 28 postimmunization sera from adults by enzyme-linked immunosorbent assay using the meningococcal standard reference serum CDC1992. The established IgG concentration in micrograms per milliliter ([IgG]g/ml) for CDC1992 against OA ؉ antigen (16.2 g/ml) was used as a reference to assign a concentration of 10.13 g/ml IgG against OA ؊ antigen by cross-standardization. Overall, the IgG assignments for these sera were higher against OA ؉ antigen (geometric mean concentration [GMC] ‫؍‬ 7.16 g/ml) than against OA ؊ antigen (GMC ‫؍‬ 2.84 g/ml). However, seven sera showed higher specific [IgG]g/ml values against the OA ؉ antigen than against the OA ؊ antigen. These sera were also distinguished by the inability of fluid-phase OA ؊ antigen to compete for antibody binding to OA ؉ solid-phase antigen. Although there was no overall difference in functional activity measured by complement-mediated serum bactericidal assay (SBA) against OA ؉ and OA ؊ target bacteria (geometric mean titers of 9,642 and 9,045, respectively), three serum specimens showed a large difference in SBA antibody titers against OA ؉ versus OA ؊ W135 target bacteria, which may reflect different epitope specificities for these sera. Our data indicate that, for some sera, the agreement in anti-OA ؉ versus anti-OA ؊ W135 IgG assignments is serum specific and does not reflect the functional (killing) activity in vitro.

Seroprevalence of Serum Bactericidal Antibodies against Group W135 and Y Meningococci in England in 2009

“…The above also holds true for capsular group Y, and a further potential factor is that the polysaccharide capsules for both groups Y and W135 can be in either an O-acetylated or de-O-acetylated form (20). For group W135, O-acetylation status was shown to impact serological measurements of antibodies directed against W135 in sera from immunized adults (15).…”

Bacterial polysaccharides as major surface antigens: interest in O-acetyl substitutions

“…Nevertheless, for some sera, the agreement in anti-O-acetyl positive versus O-acetyl negative MenW IgG assignment was serum-specific and did not reflect the functional activity in vitro. 149 An original study in mice demonstrated that MenW CPS conjugates displaying low O-acetylation levels were more immunogenic than the plain CPS and that hydrazine-mediated reduction of the O-5 acetyl groups in the MenW CPS had no adverse effect on immunogenicity nor on the CPS structure as detected by NMR.…”

Functional Antibodies to the O-Acetylated Pneumococcal Serotype 15B Capsular Polysaccharide Have Low Cross-Reactivities with Serotype 15C

“…The lack of O acetylation can contribute to a change in the antigenic structure of the capsular polymer, making it nonreactive with the anti-15B antibodies. O acetylation has been shown to be an important parameter when measuring functional antibody activity in meningococcus (2,10). With meningococcus groups C and Y, the O acetylation masks the epitopes on the Ps backbone to which functional antibody is directed (8).…”