Vaccines bacterial cell component

Bacterial cell component vaccines. Rather than... 

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. 

The TIPDS group was also one of the dramatis personae in the delicate and complex methodology used to prepare other bacterial cell wall components implicated in immunogenic mechanisms. A superb example is the synthesis of small synthetic saccharide fragments used to prepare a vaccine against Haemophilus influenzae type b (Hib), a serious infection in young children.235... 

A subunit vaccine consists of one or more immunogenic epitopes, proteins, or other components of a pathogenic organism. Immunogenic epitopes can be chemically synthesized and are known as peptide vaccines, e.g., peptide vaccine candidates for foot-and-mouth disease virus. The pathogen could be disrupted, and one or more immunogenic proteins such as bacterial cell wall proteins flagella or pili and viral envelope, capsid, or nucleoproteins can be purified. The isolation of such components in purified form is sometimes cumbersome and expensive. However, bacterial exotoxins can be easily purified, inactivated, and used as toxoid vaccines. 

For Lot B the acellular pertussis vaccine components are produced from B. pertussis cultures grown in Stainer-Scholte medium modified by the addition of casamino acids and dimethyl-betacyclodextrin. Fimbriae types 2 and 3 are extracted from the bacterial cells and the pertussis toxin, FHA, and PRN are prepared from the supernatant. These proteins are purified by sequential filtration, salt precipitation, ultrafiltration, and chromatography. Pertussis toxin is inactivated with glutaraldehyde and FHA is treated with formaldehyde. The individual antigens are adsorbed separately onto aluminum phosphate. Diphtheria and tetanus, toxoids are individually adsorbed onto aluminum phosphate. The adsorbed diphtheria, tetanus, and acellular pertussis components are combined in a sterile isotonic sodium chloride solution containing 2-phenoxyethanol as preservative. Each dose contains 10 pg of PT, 5 pg of FHA, 3 pg of PRN, 5pg of FIM, as well as 15Lf of diphtheria toxoid and 5.0 Lf of tetanus toxoid. 

In the early 20th century it was recognized that some components of a microbacterial cell were more important than others for protection and thus came the concept of subunit vaccines. When combined with the discovery that bacterial toxins could be inactivated with formaldehyde, the result was the introduction of a diphtheria subunit vaccine in 1923 and a tetanus subunit vaccine in 1927. 

Although there are a number of advantages associated with the use of subunit vaccines (e.g., highly purified peptides, proteins or DNA) as vaccines (e.g., specificity), one feature they all have in common is that they are generally poorly immunogenic. The more traditional vaccines contain many other components, some of which elicit additional T-cell assistance or function as adjuvants. An adjuvant is a substance that acts as an immunostimulator, one example being the bacterial DNA in a whole cell vaccine. The overall result is a more robust immune response than that provided by the antigen alone. 

Bacterial DNA, long a component of the earlier whole cell vaccines, has been shown to have an immunostimulatory effect on immune cells and is a potent inducer of cytokines such as IL-1, IL-6, and IL-12. Monophosphoryl A, a component of mycobacterial cell walls, reacts with receptors on antigen producing cells and generates a Thl response due to the production of IL-2 and IFN-y. 

Biological sources are primarily used for vaccines. Vaccines are suspensions of living or killed micro-organisms, components or products thereof. They are produced in living systems. Eggs are the most widely used medium at present, notably for influenza vaccines, but there is increasing use of animal cell cultures. Bacterial vaccines, for example, the diphtheria vaccine, can be cultured. There is an overlap here with fermentation processes (Section II.D.). 

Cellular products, including products composed of human, bacterial or animal cells (such as pancreatic islet cells for transplantation), or from physical parts of those cells (such as whole cells, cell fragments, or other components intended for use as preventative or therapeutic vaccines). 

Future cultivation methods will resemble existing methods of microbial and virus culture. Ill-defined medium components and cells will be replaced to enhance reproducibflity in production. For bacterial and ex vivo cultivated virus, analytical advances will make monitoring the environment and nutritional status of the culture more ubiquitous. However, the major changes will be in novel product types — single-molecule subunit antigens, viras-hke particles, monoclonal antibodies, and gene-therapy vaccines, each of which will incorporate novel processes. 

Traditional vaccines mainly consisted of live attenuated pathogens, whole inactivated orj nisms, or inactivated bacterial toxins. Many traditional vaccines based on pathogen whole cells often contain components that can cause toxicity related side effects. As a result... 

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