Short-chain lipopolysaccharide mutants of serogroup B Neisseria meningitidis of potential value for production of outer membrane vesicle vaccines.
Four lipopolysaccharide (LPS) mutants (Mu-1 to Mu-4) were isolated after exposing Neisseria meningitidis strain 44/76 to pyocins from Pseudomonas aeruginosa. Parent strain LPS contained one major SDS-PAGE band expressing the immunotype determinants of L3, L3,7 and L3,7,9 and a minor band of higher mobility expressing the immunotype determinants of L8, L8a, L1,8,10 and L11. Each mutant LPS appeared as one SDS-PAGE band of higher mobility than the bands of the parent strain. None of these LPSs expressed the immunotype determinants of the parent strain, except Mu-4 LPS which reacted with the L11-specific MAb 4C4. Strain 44/76 LPS was found to contain galactose (Gal), glucose (Glc), heptose (Hep), glucosamine (GlcN), and 2-keto-3-deoxy-octulosonic acid (Kdo) in the molar ratios of 1.9:1.3:1.7:3.5:2.1. The corresponding ratios of the mutants were: Mu-4, 0:1.7:1.7:2.8:2.0; Mu-3, 0:0:1.7:2.4:1.6; Mu-2, 0:0:2.1:1.8:2.0, Mu-1, 0:0:1.8:1.9. Thus, all mutant LPSs lacked Gal and possessed less GlcN as compared to strain 44/76 LPS. Consequently, these mutants do not express the lacto-N-neo-tetraose (Gal1-4GlcN1-3Gal1-4Glc) commonly found as a part of meningococcal LPS and also on structures of human erythrocytes. These LPS mutants will be considered for use in production of OMV vaccines without host-like antigens, which might favour induction of antibodies to more conserved epitopes of meningococcal LPS.
Andersen
S R
SR
Department of Vaccinology, National Institute of Public Health, Oslo, Norway.
Bjune
G
G
Lyngby
J
J
Bryn
K
K
Jantzen
E
E
D000907:Antibodies, Bacterial / Q000276:immunology; D000911:Antibodies, Monoclonal / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000032:analysis; D001428:Bacterial Vaccines / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D002240:Carbohydrate Sequence; D006801:Humans; D008070:Lipopolysaccharides / Q000737:chemistry* / Q000276:immunology; D008969:Molecular Sequence Data; D009154:Mutation; D009345:Neisseria meningitidis / Q000737:chemistry / Q000235:genetics* / Q000276:immunology; D011709:Pyocins / Q000494:pharmacology; D012703:Serotyping
D000907:Antibodies, Bacterial; D000911:Antibodies, Monoclonal; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D008070:Lipopolysaccharides; D011709:Pyocins; C074517:opc protein, bacteria