Bacterial vaccines pertussis vaccine

The single-component bacterial vaccines are listed in Table 15.1. For each vaccine, notes are provided of the basic material fkm which the vaccine is made, the salient production processes and tests for potency and for safety. The multicomponent vaccines that are made by blending together two or more of the single component vaccines are required to meet the potency and safety requirements for each of the single components that they contain. The best known of the combined bacterial vaccines is the adsorbed diphtheria, tetanus and pertussis vaccine (DTPerWac/Ads) that is used to immunize infants, and the adsorbed diphtheria and tetanus vaccine (DTWac/Ads) that is used to reinforce the immunity of school entrants. 

Killed (bacterial) vaccine Typhoid, cholera, pertussis, plague, meningitis. 

To some extent the simplest vaccines are those in which the bacterial or viral pathogens has been killed by chemicals or heat so that they themselves cannot cause disease but can confer protection against invasion. This has been used, for example, for the combined diphtheria-tetanus-pertussis vaccine. In this case there were concerns about the presence of entire cells that could cause complications other than the needed protection. Recently acellular systems have been introduced which may... 

Various bacterial vectors have been used to express a number of bacterial B. pertussis, S. pneumoniae, Y. pestis, and L. monocytogenes), viral (herpesvirus, influenza virus, human immunodeficiency virus, simian immunodeficiency virus, and hepatitis B virus), and parasitic (5. mansoni, and L. major) antigens. Significant improvements in attenuation of bacteria, and the stability, localization, and expression levels of heterologous antigens are required to market the bacterial vector-based vaccines for use in humans or animals. 

The pertussis vaccine is another example where, traditionally, whole bacterial cells have been used, but recent developments have led to an acellular pertussis vaccine that may contain detoxified toxin, either alone or combined with several other bacterial antigens. 

Acellular pertussis vaccines contain selective components of the B. pertussis organism. All acellular vaccines contain pertussis toxin (PT), and some contain one or more additional bacterial components (e.g., filamentous hemagglutinin [FHA], pertactin [a 69-kDa outer membrane protein], and fimbriae types 2 and 3). Acellular pertussis vaccine is recommended for all doses of the pertussis schedule at 2, 4, 6, and 15 to 18 months of age. A fifth dose of permssis vaccine is given to children 4 to 6 years of age. Pertussis vaccine is administered in combination with diphtheria and tetanus (DTaP). Although the permssis vaccine is not recommended for individuals 7 years of age and older, booster doses for adolescents and adults may be incorporated into future recommendations because members of these groups are important reservoirs of infection. 

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. 

Future immunizations are likely to rely less on whole virus or bacterial vaccines and more on acellular or subunit vaccines. Side effects resulting from the pertussis vaccine, generally mild fever or inflammation but occasionally a more serious problem, led to the development of an acellular pertussis vaccine using only bacterial proteins. Similar vaccines, some containing only genetic information for production of viral proteins, are likely to be used s ainst other diseases in the future. 

A detailed description of aU the aspects of traditional bacterial vaccine manufacture may be found in the World Health Organization technical report series for the production of whole-ceU pertussis, diphtheria, and tetanus toxoid vaccines ... 

A number of B. pertussis (polypeptide) antigens have been expressed in E. coli and other recombinant systems. Several of these are being evaluated as potential subunit vaccines, including B. pertussis surface antigen, adhesion molecules and pertussis toxin. Pertussis toxin has been shown to protect mice from both aerosol and intracerebral challenge with virulent B. pertussis. The bacterial proteins that mediate surface adhesion protect mice from aerosol but not intracerebral challenge. Future pertussis subunit vaccines may well contain a combination of two or more pathogen-derived polypeptides. 

Bacterial toxins such as diphtheria and tetanus can damage host cells but the isolated toxins can also be immunogenic. However, the induced response may not always be very strong and booster shots are required every 10 years. Adjuvants could improve the response and both diphtheria and tetanus toxoids are more effective when combined with pertussis subunit vaccines, the DPT combination at present used clinically. 

Diphtheria, Tetanus, and Pertussis. These vaccines in combination (DTP) have been routinely used for active immunization of infants and young children since the 1940s. The recommended schedule calls for immunizations at 2, 4, and 6 months of age widi boosters at 18 months and 4-5 years of age. Since 1993 these vaccines have been available in combination with a vaccine that protects against Haemophilus disease, thus providing protection against four bacterial diseases in one preparation. A booster immunization with diphtheria and tetanus only is recommended once every 10 years after the fifth dose. 

Cholera vaccines are produced by inactive bacteria and are administered subcutaneously, intramuscularly, or intradermally. Cholera vaccines should not be administered intradermally in children less than 5 years of age. The vaccination is particularly indicated for people living in highly endemic areas, as well as laboratory and medical personnel exposed to Vibrio cholerae. Diphtheria tetanus pertussis (DTP) vaccine can be made either as toxoids or inactivated whole bacteria. Hemophillus influenzae vaccine is a bacterial polysaccharide conjugated to proteins and is given as one intramuscular dose. A booster dose is not recommended. This vaccine is given to all children in cases such as plenia and other at-risk condiUons. 

Detoxification. The process by which bacterial toxins are converted to harmless toxoids. Formaldehyde is used to detoxify the toxins of Corynebacterium diphtheriae, Clostridium botu-linum and Cl. tetani. The detoxification may be performed either on the whole culture in the fermenter or on the purified toxin after fractionation. Traditionally the former approach has been adopted, as it is much safer for the operator. However, the latter gives a purer product. The pertussis toxin used in acellular vaccines may be detoxified with formaldehyde, glutaraldehyde, or both, hydrogen peroxide or tetranitromethane. In the case of genetically detoxified pertussis toxin, a treatment with a low concentration of formaldehyde is still performed to stabilize the protein. 

Appropriate immunizations should be a primary consideration in the prevention of infections in HSCT recipients. Immunizations against common bacterial and viral pathogens are timed to avoid periods of severe immunosuppression following HSCT when the protective response to vaccination potentially would be decreased. Current recommendations for immunization of HSCT patients include three doses each of diphtheria-pertussis-tetanus or diphtheria-tetanus, inactivated polio, conjugated H. influenzae type b, and hepatitis B vaccines at 12, 14, and 24 months after transplantation. The 23-valent pneumococcal vaccine should be administered at 12 and 24 months after HSCT, and the influenza vaccine should be administered prior to HSCT, resumed at least 6 months after transplantation, and con-... 

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