Complex of Meningococcal Group B Polysaccharide and Type 2 Outer Membrane Protein Immunogenic in Man

Abstract

A B S T R A C T A noncovalent complex of meningococcal group B polysaccharide and type 2 outer membrane protein has been characterized and its potential as a vaccine against group B meningococcal disease investigated. The polysaccharide component was found to have a partition coefficient, Kd, of 0.34 on Sepharose CL-4B in the presence of sodium deoxycholate. The protein consisted of four to five major proteins including the principal outer membrane protein. Hydrophobic binding between the protein and polysaccharide was demonstrated by gel filtration and isopycnic CsCl density gradient centrifugation and found to involve all of the proteins. After demonstrating safety and immunogenicity in animals, two lots of vaccine were tested in a total of eight volunteers. Two 120-,ug doses were given subcutaneously at 0 and 5 wk. Mild local reactions occurred in all eight volunteers, but no systemic reactions were observed. 2 wk after the first dose, six of the volunteers had increased levels of bactericidal antibodies against both the group B polysaccharide and the outer membrane proteins. Antibody rises to the group B polysaccharide (mean 6-fold) were confirmed by passive hemagglutination assays and rises to the proteins (mean 10-fold) by a solid phase radioimmunoassay. The second dose resulted in little or no increase in antibody titers. Antibody titers declined over a period of 14 wk but mostly remained above preimmunization levels. Bactericidal antibodies with specificity for the group B polysaccharide were mostly of the immunoglobulin (Ig)M class, and were directed against a determinant associated only with high molecular weight polysaccharides. We conclude that both the group B polysaccharide and the outer membrane protein are immunogenic in man when presented as a complex and that the complex warrants further testing and development as a vaccine against group B meningococcal disease.

TREM-2 binds to lipooligosaccharides of Neisseria gonorrhoeae and is expressed on reproductive tract epithelial cells

“…MkC Δ1-5 is an isogenic mutant of MkC expressing LOS containing a truncated OS α chain (26). LOS was isolated by hot phenol extraction and outer membrane complexes (OMC) containing both LOS and proteins were prepared as described previously (28,29). For some experiments, LOS was O-deacylated with anhydrous hydrazine as reported previously (30), which removes the O-linked β-hydroxylaurate acyl chains of lipid A while leaving the two N-linked β-hydroxymyristate chains intact.…”

Immunoglobulin allotypes and immune response to meningococcal group B polysaccharide.

“…Several recent observations by us and others suggest that such genes also exist in man (2)(3)(4). The data presented here indicate the existence of an allotype-linked Ir gene(s) that regulates the humoral immune response to meningococcal polysaccharide (MPS) group B. Group B Neisseria meningitidis continues to be responsible for a major proportion of meningococcal disease in the United States, Europe and England (5). Protection from meningococcal disease has been correlated with the presence of serum bactericidal antibodies (6).…”

Immunogenic and protective properties of meningococcal serotype 2a protein in the hen-embryo model

“…The serotype 2 protein extracted from strain M986 (B, 2a) is protective in animal models Craven and Frasch, 1979) but does not appear to be a satisfactory immunogen in humans (Zollinger et al, 1978;Frasch, 1979). However, a more soluble protein, or protein complexed with group B polysaccharide appear to be more promising as vaccines (Zollinger et al, 1979;Peppler and Frasch, 1982). On the basis of recent observations that serotype 2b meningococci are more prominently associated with group B disease than are serotype 2a meningococci Poolman et al, 1980), and the results of the present study showing that protein extracted from strain M986 provided limited protection against serotype 2b meningococci, it seems important that a complex of group B polysaccharide and outer membrane proteins extracted from both serotype 2a and 2b meningococci should be investigated as a vaccine that would provide the broadest protection against serotype 2 meningococci.…”

“…Unfortunately, group B capsular polysaccharide is not immunogenic in man (Wyle et al, 1972); consequently meningococcal non-capsular cell surface antigens including protein and complexes of protein and group B polysaccharide are being investigated as possible vaccines against disease caused by group B meningococci (Zollinger et al, 1978;Frasch, 1979;Zollinger et al, 1979;.…”