title: De-N-acetylated sialic acid is immunogenic and elicits antibodies that are protective against Neisseria meningitidis.
abstract: Recently, we showed that monoclonal antibodies (mAbs) that are reactive with derivatives of polysialic acid containing de-N-acetylated neuraminic acid (Neu) residues are protective against N. meningitidis group B strains (Moe et al. 2005, Infect Immun73: 2123; Flitter et al., in preparation). In addition, we found that fully de-N-acetylated PSA (i.e. poly alpha 2,8 Neu) conjugated to tetanus toxoid (DeNAc) elicits IgM and IgG antibodies of all subclasses in mice that bind to group B strains, activate human complement deposition, are protective in an infant rat model of meningococcal bacteremia and are bactericidal against group C strains (Moe et al, in press). We show here that anti-DeNAc mAbs, DA1 and DA2 (both IgM), are reactive with polysaccharides containing Neu, bind to group B, C, W135 and Y but not X strains grown in chemically defined media (CDM). However, when the group X strain is grown in CDM supplemented with human plasma, DA2 binds. Also both mAbs mediate bactericidal activity against B, C, W135, and X strains with human complement. The results suggests that N. meningitidis express and/or acquire zwitterionic de-N-acetyl sialic acid antigens that can be the target of protective antibodies.
authors.affiliation: Center for Immunobiology and Vaccine Development, Children's Hospital & Research Center Oakland, Oakland, CA 94609.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Moe
authors.forename: Becca A
authors.initials: BA
authors.lastname: Flitter
authors.forename: Jessica Y
authors.initials: JY
authors.lastname: Ing
authors.forename: Tamara S
authors.initials: TS
authors.lastname: Bhandari
authors.forename: Hardeep
authors.initials: H
authors.lastname: Kaur