Polysaccharides Haemophilus influenzae type

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. 

In the cell-wall antigen from Staphylococcus aureus M, taurine is linked as an amide (51) to a 2-acetamido-2-deoxy-D-galactosyluronic residue. l-Threonine and L-glutamic acid are linked as amides to D-glucuronic acid residues in the LPS from Rhodopseudomonas sphaeroides ATCC 17023 and in the capsular polysaccharide from Klebsiella K82, respectively. In the capsular polysaccharide from E. coli K54, L-serine and L-threonine, in the ratio 1 9, are linked to the carboxyl group of a D-glucuronic acid residue. In the capsular polysaccharide from Haemophilus influenzae type d,... 

In different polysaccharides of the teichoic acid type, monosaccharides or oligosaccharides are connected by phosphoric diester linkages. Two examples are the capsular antigens from Neisseria meningitides type A (56) and Haemophilus influenzae type c (57), respectively. Glycerol phosphate... 

Haemophilus influenzae type b Cultures of H. influenzae type b 1 Separation of capsular polysaccharide 2 Conjugation with a protein Estimation of capsular polysaccharide content ... 

V. Verez-Bencomo, V. Femandez-Santana, E. Hardy, M. E. Toledo, M. C. Rodriguez, L. Heynngnezz, A. Rodriguez, A. Baly, L. Herrera, M. Izquierdo, A. Villar, Y. Valdes, et al., A synthetic conjugate polysaccharide vaccine against Haemophilus influenzae type b, Science, 305 (2004) 522-525. 

Haemophilus influenzae type b (Hib) vaccines currently in use are conjugate products, consisting of either a polysaccharide or oligosaccharide of polyribosylribitol phosphate (PRP) covalently linked to a protein carrier. 

Despite their popularity, aluminium-based adjuvants suffer from several drawbacks. They tend to effectively stimulate only the humoral arm of the immune response. They cannot be frozen or lyophylized, as either process promotes destruction of their gel-based structure. In addition, aluminium-based products display poor or no adjuvanticity when combined with some antigens (e.g. typhoid or Haemophilus influenzae type b capsular polysaccharides). 

Each lyophilisate for one immunising dose of diphtheria, tetanus toxoids and pertussis with Haemophilus b conjugate vaccine contains Haemophilus influenzae type b polysaccharide conjugated to tetanus protein 10 meg, purified diphtheria toxoid 1 immunising dose, purified tetanus toxoid 1 immunising dose, Bordetella pertussis minimum of 4.1 lU. 

Kayhty, H., V. Karanko, H. Peltola, and P.H. Makela, Serum antibodies after vaccination with Haemophilus influenzae type b capsular polysaccharide and responses to reimmunization no evidence of immunologic tolerance or memory. Pediatrics, 1984. 74(5) 857-65. 

A sulfur-based chemoselective method was applied to the synthesis of a conjugate polysaccharide vaccine against Haemophilus influenzae type b.37 The... 

Haemophilus influenzae type b conjugate (Hib) Bacterial polysaccharid e conjugated to protein Intramuscular One dose (see Table 1-2 for childhood schedule) Not recommende d 1. For all childr en 2. Asple nia and... 

Werz DB and Seeberger PH. Carbohydrates as the next frontier in pharmaceutical research. Chem Eur J, 2005 11(11) 3194-3206. Verez-Bencomo V, Fernandez-Santana V, Hardy E, Toledo ME, Rodriguez MC, Heynngnezz L, et al. A synthetic conjugate polysaccharide vaccine against Haemophilus influenzae type b. Science 2004 305 522-525. 

Kanra, G. Yurdakok, K. Ceyhan, M. Ozmert, E. Turkay, F. Pehlivan, T. Immunogenicity and safety of haemophilus influenzae type B capsular polysaccharide tetanus conjugate vaccine (PRP-T) presented in a dualchamber syringe with DTP. Acta Paediatr. Jpn. 1997, 39, 676-680. 

Weinberg GA, Granoff DM. Polysaccharide-protein conjugate vaccines for the prevention of Haemophilus influenzae type b disease. J Pediatr 1988 113(4) 621-31. 

Capsular polysaccharide of bacteria is one of the significant targets for development of vaccines [128]. For example, Haemophilus influenza type B (Hib) vaccine, made of a polysaccharide-protein conjugate, is now used worldwide as a highly effective therapy [129]. Verez-... 

Some examples of research under development include a synthetic conjugated polysaccharide vaccine against Haemophilus influenzae type B, which has been described in 2004 (O Fig. 34). The vaccine prototype was obtained by conjugation to human serum albumin (HSA) [173]. Furthermore, very recently a malaria vaccine has been suggested [174] which is based on the total synthesis of the malaria toxin responsible for the morbidity and mortality associated with malaria. The malaria parasite expresses a large amount of glycosylphosphatidylinositol... 

For some polysaccharides as for example Nm group C [99] and H. Influenzae type b [100] the periodic oxidation occurs selectively at a position leading to fragmentation of the CPS. Depolymerized CPSs are further modified for activation. The following examples of Haemophilus influenzae type b CPS modification illustrate very well the broad spectrum of present technology [101] (see Scheme 2). 

Contains 5 meg 0.5 ml HBsAg and 7.5 meg Haemophilus influenzae type B purified capsular polysaccharide fragments conjugated to 125 meg Neisseria meningitidisouler membrane protein complex. 

P. Branefors-Helander, Structural studies of two capsular polysaccharides elaborated by strains of Haemophilus influenza type e, Carbohydr. Res., 88 (1981) 77-84. 

Haemophilus influenzae type b conjugate Bacterial polysaccharide conjugate For all children, asplenics, and others at risk... 

Schneerson R, Barrera O, Sutton A, Robbins JB. Preparation, characterization, and immunogenicity of Haemophilus influenzae type b polysaccharide-protein conjugates. J Exp Med 1980 152 361-376. 

Fully methylated and fully acetylated disaccharides isolated from the capsular polysaccharide of Escherichia coli KlOO and Haemophilus influenzae type b have been identified by m.s. as 2-0- and 1-O-D-ribofuranosyl ribitol, respectively. " The capsular antigen of H. influenzae type c has been purified by ion-exchange chromatography. Structural investigations have identified the disaccharide (8) as the repeating unit of the polysaccharide. 

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