Antigenicity of dextran-protein conjugates in mice. Effect of molecular weight of the carbohydrate and comparison of two modes of coupling

Abstract

Protein conjugates of polysaccharides or their breakdown products are being used as improved "T-dependent" vaccines. We tried to define optimal characteristics of future conjugate vaccines by testing the immunogenicity of thirteen conjugates of alpha 1-6 dextran and chicken serum albumin in mice (BALB/c and CBA). All conjugates induced stronger antidextran antibody responses than the polysaccharide, and a fair proportion of these antibodies were IgG. However, there was a range of antigenicities. Consistently strong responses were obtained with conjugates that carried small dextran molecules (m.w. 1000 to 4000) coupled to the protein via the reducing end. Modification of such an "optimal" conjugate either by increasing the size of the saccharide to 40,000 Da, or by permitting multiple attachments of the saccharide molecule to the protein, reduced its antigenicity. Carbohydrate/protein ratios varying from 0.17 to 0.49 were associated with excellent antidextran responses.