Adjuvant effect of bacterial LPS and/or alum precipitation in responses to polysaccharide and protein antigens

Abstract

A conjugate of a hapten (NIP) and a strongly antigenic protein chicken gamma globulin (CGG), when injected in soluble form into mice, induced weak primary responses, as weak as responses induced by conjugates of NIP (or other haptens) to polysaccharides Ficoll or alpha (-1-6) dextran. Mean concentrations of anti-hapten antibodies on day 14 varied within the range of 37-105 micrograms/ml (C57BL mice) or 14-38 micrograms/ml (CBA mice). The NIP-protein conjugate administered in alum-precipitated form induced 100 times higher primary antibody responses. Alum-precipitation of NIP-Ficoll made it a modestly stronger antigen than soluble NIP-Ficoll. When lipopolysaccharide (LPS) was injected together with any of the soluble antigens, the mice produced plenty of anti-hapten antibodies regardless of whether the antigen was hapten-polysaccharide or hapten-protein conjugate. Concentrations on day 14 varied from around 400 micrograms/ml to approximately 1600 micrograms/ml. LPS had a similar adjuvant effect on antidextran responses. LPS alone induced a polyclonal immunoglobulin production, and the immunoglobulin produced included 'anti-NIP' or 'anti-dextran' detectable in the solid phase antibody assay. These 'antibodies' induced by LPS alone were almost totally mercapto-ethanol-sensitive and poorly detectable by Farr assay or the bacteriophage assay. The response to the LPS+antigen combination was specific for the antigen and included both mercapto-ethanol-sensitive and resistant antibodies.