Studies on Immunogenicity of -2,8-Linked N-Glycolylneuraminic Acid Polymers

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In 1978, Inoue and Iwasaki discovered a novel class of sialoglycoproteins in rainbow trout eggs. The most striking feature of these glycoproteins is the presence of oligo(poly)sialyl chains, and we named them polysialoglycoproteins (PSGP). We have shown that PSGP is a ubiquitous component of the eggs of all species of salmonid fishes examined. This study was undertaken to elicit antibodies against polysialic acids because <alpha>-2,8-linked homopolymer of N-acetylneuraminic acid (NeuAc) structure occurring in the group B meningococci (Neisseria meningitidis) is pathogenic. <alpha>-2,8-Linked poly(NeuAc) is known to be extremely poor immunogen in various animals including human. Rainbow trout egg PSGP contains exclusively N-glycolylneuraminic acid (NeuGc), so that we used it as the immunogen to raise <alpha>-2,8-linked poly(NeuGc) antibodies in rabbits and BALB/c mice. We continued the antigen injection for 16 months, but there was np detectable antibodies in the serum of all animals us … More ed. The observed poor immunogenicity is ascribed, at least in part, to the presence of molecules having similar or identical structures in the host animals so that immunization would likely be suppressed by immune tolerance. Recently, we succeeded in eliciting anti-(rainbow trout PSGP) antiserum in chicken. We also examined the immunoreactivity of <alph>-2,8-linked poly(NeuGc) chains against a unique antiserum ("H-46"), obtained by J.B.Robbins (N.I.H.) after taking for 7 years by immunizing a horse using formalin-treated group B meningococci as immunogen. H.46 antiserum containing polyclonal IgM antibodies has been proven not to form immunoprecipitin bands against <alpha>-2,8-linked poly(NeuGc). It can thus be concluded that H.46 binds specifically to <alpha>-2,8-linked poly(NeuAc) and can onlybe used as a probe for poly(NeuAc). In this respect, our results on chicken, though preliminary, may provide the specific antibody against poly(NeuGc) which may possibly be used as a diagnostic tool for detecting poly(NeuGc) in a variety of animal tissues. Less