Vaccines bacterial capsular polysaccharides

Modem subunit vaccines contain one or more selected antigenic subunits that have been found to provide protection against a particular pathogen. They are better defined from a physicochemical aspect and have fewer side effects than vaccines, which contain intact cells, whether inactivated or attenuated. Current subunit antigens include viral and bacterial proteins as well as bacterial capsular polysaccharides. 

Because the classical pathway has a requirement for polysaccharide-specific antibody, and because the process of producing this antibody takes a few days, the host is compromised during the initial, acute stages of bacterial infection, and is liable to die, or to acquire serious morbidity effects. Thus, the rationale behind vaccination with capsular polysaccharides is to maintain a long-lasting, effective level of polysaccharide-specific antibody in the host. 

The dramatic success of antibiotics for therapeutic control of many microbial infections has tended to overshadow the value of immunochemical approaches. The article by Jennings (Ottawa, Canada) provides an up-to-date discussion of the structures of a variety of bacterial capsular polysaccharides, and serves to emphasize the important uses that such compounds have as human vaccines. 

Vaccines have been prepared traditionally by use of viruses or organisms killed by compounds such as formaldehyde or by attenuated viruses or live organisms. These are selected for a low degree of virulence after repeated passages through live animals or cell cultures. Newer methods utilize purified viral proteins, bacterial capsular polysaccharides, or... 

It has been possible to produce vaccines to use for immunization against certain bacterial infections and other human diseases. Staphylococcus aureus capsular polysaccharide in combination with a carrier protein has been used to prepare monovalent vaccines specific for S. aureus [86], The vaccine was administered to groups of healthy adults and to patients with end-stage renal disease. The antibodies are directed at the polysaccharide moiety of the glycoconjugate. The data of this study show that conjugate-induced antibodies to S. aureus can provide partial protection against S. aureus bacteremia, Fig. (45). 

Capsular polysaccharides purified from bacteria are almost non-toxic and considerably less toxic than the whole-cell and elicited anti-polysaccharide antibodies at a single dose of 10-50 pg [17]. The antibodies provide type-specific immunity lasting for several years in healthy humans [18]. The simplicity of polysaccharides as vaccines and its low toxicity prompted development of the first polysaccharidic pneumococcal vaccine (tetravalent) marketed as early as 1946 [19]. Polysaccharide vaccines were only really introduced during the 1970s to counteract the emergence of bacterial resistance to antibiotics. 

The field is actually in a good position to contribute to the development of bacterial polysaccharide glycoconjugate vaccines. Numerous fragments of capsular polysaccharides, lipopolysaccharides, or other bacterial carbohydrates have been synthesized and their protein conjugates obtained [87]. 

The starting point for the production of all microbial vaccines is the isolation of the appropriate infectious agent. Such isolates have usually been derived from human infections and in some cases have yielded strains suitable for vaccine production very readily in other instances a great deal of manipulation and selection in the laboratory have been needed before a suitable strain has been obtained. For example, bacterial strains may need to be selected for high toxin yield or production of abundant capsular polysaccharide viral strains may need to be selected for stable attenuation. 

Meningococcal vaccine is a bacterial vaccine that induces production of bactericidal antibodies specific to capsular polysaccharides of serogroups A, C, Y, and W-135. 

Selander B, Kayhty H, Wtdege E et al. Vaccination responses to capsular polysaccharides of Neisseria meningitidis and liaemophilus influenzae Type b in two C2-deficient sisters alternative pathway-mediated bacterial killing and evidence for a novel type of blocking IgG. J Clin Immunol 2000 20 138-149. 

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