Polysaccharides antigenicity

There are a number of practical problems involved with using polysaccharides as vaccines as there are frequently too many different chemotypes for it to be practicable to prepare a vaccine. In some cases a limited number of serotypes are the dominant cause of infection and it may then be possible to produce vaccines. A major problem is the poor immune response elicited by polysaccharide antigens, which may in some cases be improved by chemical modification. This is (fie case for vaccines for Haemophilus influenzae type b (a causative agent of meningitis), where the antigenicity of the polysaccharide can be increased by coupling to proteins. 

Fractionation. The process by which components are extracted firm bacterial eells or from the medium in whieh the baeteria are grown and obtained in a purified form. The polysaccharide antigens of Neisseria meningitidis are separated from the bacterial cells by treatment with hexadecyltrimethylammonium bromide and those of Streptococcus pneumoniae with ethanol. The purity of an extracted material may be improved by resolubilization in a suitable solvent and precipitation. After purification, a component may be dried to a powder, stored indefinitely and, as required, incorporated into a vaccine in precisely weighed amounts at the blending stage. 

There are two pneumococcal vaccines, a 7-valent conjugated vaccine for children younger than 6 years of age and a 23-purified-capsular polysaccharide antigen vaccine for adults. The 23 capsular types in the vaccine represent at least 85% to 90% of the serotypes that cause invasive pneumococcal infections among children and adults in the United States.41 After vaccination, an antigen-specific antibody response, indicated by a twofold or greater rise in serotype-specific antibody, develops within 2 to 3 weeks in 80% or more of healthy young adults.42... 

Live attenuated strains of measles virus Purified surface polysaccharide antigens of one or more strains of Neisseria meningitidis... 

Formaldehyde-killed Yersinia pestis Mixture of purified surface polysaccharide antigens obtained from differing serotypes of Streptococcus pneumoniae Live attenuated strains of poliomyelitis virus... 

Chelvarajan, R.L., et al. Defective macrophage function in neonates and its impact on unresponsiveness of neonates to polysaccharide antigens, J. Leukoc. Biol., 75, 982, 2004. 

Vaccines Pneumococcal vaccine, polyvalent, 23 types of S. pneumoniae PNU-Immune- 23 0.5 ml dose contains 26 pg polysaccharide antigen purified from 23 serotypes of S. pneumoniae IM,SC NA NA NA Single 0.5 ml dose NA NA... 

C-N.m.r.-spectroscopic analyses have been successfully made for determination of the position of O-acetyl groups in sialic acids, using the 9-O-acetyl- and 4,9-di-O-acetyl derivatives of Neu-/3-Me methyl ester as model compounds,9 1 or in the sialic acid residues of polysaccharide antigens ofN. meningitidis.166 1... 

MURINE MYELOMA IMMUNOGLOBULINS WITH POLYSACCHARIDE ANTIGENS ... 

Like with the KDO containing K-polysaccharides, one can observe also in this group of polysaccharides antigen modification by O-acetylation the K1 antigen and the K2 antigen occur in non acetylated and in acetylated forms (14, 18). Bacteria with the non acetylated polymers (Klac" and K2a) seem to be more pathogenic. 

Bhattacharjee, A.K., Jennings, H.J., Kenny, C.P., Martin, A. and Smith I.C.P. (1975) Structural determination of the sialic polysaccharide antigens of Neisseria meningitidis serogroup B and C with carbon 13 nuclear magnetic resonance. J. Biol. Chem. 250 1926-1932... 

Lifely, M.R., Gilbert, A.W. and Moreno, C. (1981) Sialic acid polysaccharide antigens of Neisseria meningitidis and Escherichia coli esterification between adjacent residues. Carbohydr. Res. 94 193-203... 

Gross, R.J., Cheasty, T. and Rowe, B. (1977) Isolation of bacteriophages specific for the K1 polysaccharide antigen of Escherichia coli. J. Clin. Microbiol. 6 598-550... 

However, the molecular weight, for example, may vary from 15,000 (hen egg white lysozyme) to 2,000,000 (keyhole limpet hemocyanin) daltons. Protein antigens function as the most potent immunogens, and polysaccharide antigens rank second. For cell-mediated immunity, only proteins serve as immunogens. Certain nucleic acid types such as Z-DNA and other molecules can also stimulate antibody production. 

The colitose-containing repeating unit of the E. coli 0111 polysaccharide antigen has been the subject of some synthetic work. The 3,6-dideoxyhexose was synthesized from... 

S. Hanessian and T. H. Haskell, Structural studies on Staphylococcal polysaccharide antigen, J. Biol. Chem., 239 (1964) 2758-2764. 

Several variations of this concept have been reported.50-52 For example, Ley and Priepke50 prepared the trisaccharide unit, which is derived from the common polysaccharide antigen of a group B Streptococci by a facile one-pot two-step synthesis (Scheme 4.18). In this... 

Correia Barbosa, S.F., Alkmin, M.G., Landgraf, I.M. Detecting polysaccharide antigen of Neisseria meningitidis group C in cerebrospinal fluid by dot-ELISA assay. Braz J Infect Dis 4 (2000) 144-150. 

Knirel, Y.A. Polysaccharide antigens of Pseudomonas aeruginosa. Crit Rev Microbiol 17 (1990) 273-304. 

Stenutz, R., Weintraub, A., Widmalm, G. The structures of Escherichia coli O-polysaccharide antigens. FEMS Microbiol Rev 30 (2006) 382—403. 

Moss RB, Hsu YP, Van Eede PH, Van Leeuwen AM, Lewiston NJ, De Lange G, Altered antibody isotype in cystic fibrtosis impaired natural antibody response to polysaccharide antigens, Pediatr. Res., 22 708-713, 1987. 

Fig. 1.—Fourier-transformed, C-N.m.r. Spectrum of the Native Polysaccharide Antigen of Group A Neisseria meningitidis. [Upper, containing (a) O-acetylated and (b) unacetylated residues, and lower, its fully O-deacetylated form.]...

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