Immunogenicity in animals of a polysaccharide-protein conjugate vaccine against type III group B Streptococcus.

Abstract

The native capsular polysaccharide of type III group B Streptococcus elicits a specific antibody response in only 60% of nonimmune human subjects. To enhance the immunogenicity of this polysaccharide, we coupled the type III polysaccharide to tetanus toxoid. Prior to coupling, aldehyde groups were introduced on the polysaccharide by controlled periodate oxidation, resulting in the conversion of 25% of the sialic acid residues of the polysaccharide to residues of the 8-carbon analogue of sialic acid, 5-acetamido-3,5-dideoxy-D-galactosyloctulosonic acid. Tetanus toxoid was conjugated to the polysaccharide by reductive amination, via the free aldehyde groups present on the partially oxidized sialic acid residues. Rabbits vaccinated with the conjugate vaccine produced IgG antibodies that reacted with the native type III group B streptococcal polysaccharide (3/3 rabbits), while rabbits immunized with the unconjugated type III polysaccharide failed to respond (0/3 rabbits). Sera from animals receiving conjugate vaccine opsonized type III group B streptococci for phagocytic killing by human peripheral blood leukocytes, and protected mice against lethal challenge with live type III group B streptococci. The results suggest that this method of conjugation to a carrier protein may be a useful strategy to improve the immunogenicity of the type III group B Streptococcus polysaccharide in human sub-

Discovery and characterization of sialic acid O-acetylation in group BStreptococcus

“…1 A and B, respectively. Of note, conventional methods for CPS purification include a basetreatment step to remove traces of contaminating group B carbohydrate (29), which would unavoidably hydrolyze Sia O-acetyl esters.…”

“…Later publications may have been missed this modification because strains with low levels of O-acetylation were studied or because NMR instruments were less sensitive. Ultimately, studies describing purification of the CPS for vaccine preparation introduced a 1-M NaOH treatment to eliminate the contaminating group B polysaccharide (29). This treatment has the undesired effect of removing O-acetyl groups on Sias.…”

Vaccines based on the cell surface carbohydrates of pathogenic bacteria

“…A recent study assessing cost-effectiveness of Men C conjugate in Canada was based on a price of CDN$50 per dose (De Wals et al 2004). The prices of complex and multivalent conjugates, such Wessels et al 1990, 1992a,b, 1996, Baker et al 1999, Paoletti et al 1999 as a pneumococcal conjugates, are particularly high, with the heptavalent pneumococcal conjugate being more than $50 per dose, and a four dose regime is required (Pai et al 2002). Thus the conjugate vaccines are relatively expensive products.…”

Toll-like receptor 2 dependent immunogenicity of glycoconjugate vaccines containing chemically derived zwitterionic polysaccharides

“…The zwitterionic PS were obtained as described by the introduction of a positive charge in the aliphatic chain of the terminal N-acetylneuraminic acid (NeuNAc) residue. The covalent attachment of the carrier protein CRM 197 or HSA to the zwitterionic PS was performed according to the protocol used for the conjugation of the native CPS (17). Experimental details and the final structure of the conjugates are explained in the SI Text.…”