Lipooligosaccharide (LOS) is one of the major surface antigens of Neisseria meningitidis. We are investigating the potential use of LOS as a vaccine against Group B meningococcal infections. LOS was polymerized and simultaneously conjugated to meningococcal outer membrane vesicles (OMV) using glutaraldehyde as a crosslinker. The weight ratio and molar ratio of LOS to OMV in the conjugate were 3:1 and 60:1 respectively. The molecular weights of the conjugates were heterogeneous, above 200,000. The polymerized LOS showed an average of 1000-fold reduction of its biological activity as determined by the Limulus amebocyte lysate assay and the galactosamine-sensitized mouse lethality assay. The immunogenicity of the LOS, LOS polymers and LOS-OMV conjugates were studied in mice without addition of any adjuvants. LOS polymers induced similar or lower antibody response than LOS, but LOS-OMV conjugates induced faster and 10-fold higher antibody response than LOS. Antibodies induced by LOS or LOS-polymers were only slightly bactericidal, while those induced by LOS-OMV were highly bactericidal. The substantial reduction of LOS toxicity by polymerization makes it possible to combining various sub/serotype OMV preparations to achieve broad protection against group B meningococcal infections.
