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 aft er exposing Neisseria meningitidis strain 44/76 to pyocins from Pseudo monas aeruginosa. Parent strain LPS contained one major SDS-PAGE band expressing the immunotype determinants of L3,L3,7 and L3,7,9 and a min or band of higher mobility expressing the immunotype determinants of L 8,L8a,L1,8,10 and L11. Each mutant LPS appeared as one SDS-PAGE band o f higher mobility than the bands of the parent strain. None of these L PSs expressed the immunotype determinants of the parent strain, except Mu-4 LPS which reacted with the L11-specific MAb 4C4. Strain 44/76 LP S was found to contain galactose (Gal), glucose (Glc), heptose (Hep), glucosamine (GlcN), and 2-keto-3-deoxy-octulosonic acid (Kdo) in the m olar ratios of 1.9:1.3:1.7:3.5:2.1. The corresponding ratios of the mu tants 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-1,0:0:0:1.8:1.9. Thus, all mutant LPSs lacked Gal and possessed less GlcN as compared to strain 44/76 LPS. Consequently, th ese mutants do not express the lacto-N-neo-tetraose (Gal1-4GlcN1-3Gal1 -4Glc) commonly found as a part of meningococcal LPS and also on struc tures of human erythrocytes. These IFS mutants will be considered for use in production of OMV vaccines without host-like antigens, which mi ght favour induction of antibodies to more conserved epitopes of menin gococcal LPS. (C) 1995 Academic Press Limited