Comparative studies on adjuvanticity of Klebsiella O3 lipopolysaccharide and its lipid A and polysaccharide fractions

Abstract

Previously, we found that Klebsiella O3 lipopolysaccharide (KO3 LPS) exhibits very strong adjuvant activity in augmenting the delayed-type hypersensitivity and antibody responses to protein antigens, and also strong ability to enlarge the regional lymph node in mice. By hydrolysis in 1% acetic acid at 100 degrees for 1 hr, KO3 LPS was dissociated into 54-60% polysaccharide fraction and 25-27% lipid A fraction. The lipid A fraction thus prepared retained lethal toxicity for mice, whereas the polysaccharide fraction was essentially non-toxic. However, neither the lipid A fraction nor the polysaccharide fraction could reproduce the strong adjuvanticity of KO3 LPS, and a simple mixture of these two fractions also failed to do so. It is therefore concluded that, for expression of the strong adjuvanticity of KO3 LPS, both the lipid A and polysaccharide moieties are indispensable and must be combined in the form of LPS. By contrast, administration of relatively large amounts of the lipid A fraction alone could elicit enlargement of the regional lymph node to the same degree as that attained by KO3 LPS. The regional lymph node-enlarging activity of the lipid A fraction in lesser amounts was enhanced by addition of the polysaccharide fraction. It is therefore likely that there is no direct correlation between adjuvant activity of the LPS or its derivatives, and their regional lymph node-enlarging activity.