Non-specific modulation of the immune response with liposomal meningococcal lipopolysaccharide: role of different cells and cytokines.

The immunomodulating action of Neisseria meningitidis lipopolysaccharide (LPS) incorporated into liposomes and the activation of different populations of immunocompetent cells or the secretion of cytokines were studied. LPS stimulated an anti-sheep red blood cell (SRBC) plaque-forming cell response in the spleen of mice after simultaneous injection of LPS and SRBC but if LPS was administered 3 days before the immunization with SRBC the response to SRBC was strongly suppressed. After the incorporation of LPS into liposomes the stimulation index was increased from 6 to 19 and the liposomal LPS did not suppress the immune response to SRBC. The incorporation of LPS into liposomes leads to enhancement of B-mitogenic properties of LPS, as liposomal LPS stimulated the proliferation of splenocytes in mice better than free LPS and has no influence on the thymocytes. The liposomal LPS induced more prolonged and significant accumulation of IgM-secreting cells in the spleen of mice in comparison with the free LPS. Liposomal LPS also induced more active accumulation of IFN-gamma in human peripheral blood mononuclear cells and less active accumulation of monokines, contributing to the realization of the toxic properties of endotoxin (IL-1 alpha, TNF-alpha, IL-6 and GM-CSF). These results demonstrated that the incorporation of N. meningitidis LPS into liposomes dramatically changed its immunomodulating activity. The data obtained are important for the construction of an adjuvant formulation for synthetic immunogens capable of inducing genetically unrestricted immune responses.

[The effect of detergents on the immunological activity of the antigens of Neisseria meningitidis serogroup B[]. / Vliianie detergentov na immunologicheskuiu aktivnost' antigenov Neisseria meningitidis serogruppy B.

The complex study of the influence of detergents of different classes and aluminum hydroxide, a traditional adjuvant, on the immunological activity of individual N. meningitidis antigens (outer membrane proteins, polysaccharide B) and the complex preparation containing all these antigens revealed that changes in the antigenic and immunogenic properties of the antigens under study depended on the degree of their purification and the character of modifying substances. Aluminum hydroxide proved to be the most active adjuvant: it stimulated immune response to both outer membrane proteins and antigens of the protein-polysaccharide complex, while decreasing the antigenicity of outer membrane proteins and polysaccharide. Detergents increased the antigenicity of outer membrane proteins, both purified and, to a lesser extent, contained in the complex; still the immune response only to the purified preparation could be stimulated.

[The sorption of a protein-polysaccharide complex isolated from Neisseria meningitidis serogroup B on aluminum hydroxide gels and the immunological activity of the sorbed preparations]. / Sorbtsiia belkovo-polisakharidnogo kompleksa, vydelennogo iz Neisseria meningitidis serogruppy B, na geli gidroksida aliuminiia i immunologicheskaia aktivnost' sorbirovannykh preparatov.

The protein-polysaccharide complex, isolated from group B N. meningitidis, is a variant of vaccine for the prophylaxis of group B N. meningitidis infection. In this investigation the influence of the complex of the physical properties of aluminium hydroxide gels, the amount of gel, pH and the duration of sorption on the process of sorption has been studied. Aluminium hydroxide has been shown to produce a stimulating effect on the response of mice to the polysaccharide and protein contained in the complex after immunization made in two injections. Gels with a smaller particle size have been found to possess greater adjuvant activity, as well as greater absorbing activity. The immunological activity of the complex, adsorbed ex tempore, has proved to be no different from that of the complex adsorbed in an hour.