Toxoid Vaccine

8 Key excerpts on "Toxoid Vaccine"

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  eBook - ePub

  Hugo and Russell's Pharmaceutical Microbiology

  • Stephen P. Denyer, Norman A. Hodges, Sean P. Gorman, Brendan F. Gilmore, Stephen P. Denyer, Norman A. Hodges, Sean P. Gorman, Brendan F. Gilmore(Authors)
  • 2011(Publication Date)
  • Wiley-Blackwell

    (Publisher)

  in vitro culture. At the same time, because they contain all components of the microorganism they can be somewhat toxic. It is thus often necessary to divide the total amount of vaccine that is needed to induce protection into several doses that are given at intervals of a few days or weeks. Such a course of vaccination takes advantage of the enhanced ‘secondary’ response that occurs when a vaccine is administered to an individual person whose immune system has been sensitized (‘primed’) by a previous dose of the same vaccine. The best-known killed vaccines are whooping cough (pertussis), typhoid, cholera, plague, inactivated polio vaccine (Salk type) and rabies vaccine. The trend now is for these rather crude preparations to be phased out and replaced by better-defined subunit vaccines containing only relevant protective antigens, e.g. acellular pertussis and typhoid Vi polysaccharide vaccines.

  2.1.3 Toxoid Vaccines

  Toxoid Vaccines are preparations derived from the toxins that are secreted by certain species of bacteria. In the manufacture of such vaccines, the toxin is separated from the bacteria and treated chemically to eliminate toxicity without eliminating immunogenicity, a process termed ‘toxoiding’.

  A variety of reagents have been used for toxoiding, but by far the most widely employed and generally successful has been formaldehyde. Under carefully controlled conditions this reacts preferentially with the amino groups of proteins although many other functional groups potentially may be affected. Ideally the toxoided protein will be rendered non-toxic but retain its immunogenicity.

  The treated toxins are sometimes referred to as formol toxoids. Toxoid Vaccines are very effective in the prevention of those diseases such as diphtheria, tetanus, botulism and clostridial infections of farm animals, in which the infecting bacteria produce disease through the toxic effects of secreted proteins which enzymically modify essential cellular components. Many of the clostridial toxins are lytic enzymes with very specific substrates such as neural proteins. Detoxification is also required for the pertussis toxin component of acellular pertussis vaccines.

  Anthrax adsorbed vaccine is not toxoided but relies on the use of cultural conditions that favour production of the protective antigen (binding and internalization factor) rather than the lethal factor (protease) and oedema factor (adenyl cyclase) components of the toxin. Selective adsorption to aluminium hydroxide or phosphate also slows release of residual toxin.

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  Development and Formulation of Veterinary Dosage Forms

  • Gregory E. Hardee, J. Desmond Baggo, Gregory E Hardee, J D Baggot, Gregory Hardee, J Baggot, Gregory E Hardee, J D Baggot(Authors)
  • 2021(Publication Date)
  • CRC Press

    (Publisher)

  Safety is also a concern in any formulation so all virus vaccines, in their final formulation, are tested at two to 10 times the recommended dose in the most susceptible animal known. If any overt clinical signs are noted or adverse reactions occur the vaccine is considered unsafe and is not offered for sale.

  IV. Bacterial Vaccines

  A. Types

  Vaccines for the prevention of disease caused by bacterial infectious agents may take one of five forms: inactivated toxin (toxoid), chemically inactivated whole organisms (bacterin), attenuated live organism (modified live), recombinant produced and/or purified cellular proteins (subunit), or live recombinant organisms. Of these, the toxoid and chemically inactivated whole organisms make up the majority of vaccines licensed for use in animals.

  Toxoids are prepared from bacteria-produced toxins, which are inactivated and used to prevent or control diseases caused by these toxins. Toxoids are used to control infections caused by members of the following genera; Pasteurella (pneumonia in cattle, pigs, and sheep); Staphylococcus (mastitis); Bordetella bronchiseptica (atrophic rhinitis in pigs); and Clostridia sp., which are responsible for causing such diseases as tetanus in horses; enterotoxemia of lambs; malignant edema of horses, cattle, sheep, and swine; black disease in sheep and sudden death in cattle and pigs. Tenanus toxoid with adjuvant is a highly potent antigen capable of inducing immunity against the tetanospasm. However, at least two doses, 4 to 6 weeks apart, are required to induce solid immunity in the horse. This immunity must be reinforced at yearly intervals to ensure that protective immunity is maintained. The use of toxoids to control disease in companion animals (dogs and cats) is relatively rare.

  Inactivated whole bacterial cell suspensions are probably the most common type of vaccine used in domestic animals. They are generally administered once or twice annually. These vaccines have historically been extremely effective and safe to use in young or pregnant animals. Vaccines prepared in this manner proved highly effective in protecting against respective diseases. Such was the case with early Leptospira vaccines that were prepared from one serovar and provided protection against only that offending serovar. These vaccines provide only short-term immunity with highly specific efficacy. However, whole-cell vaccines prepared from gram-negative organisms (i.e., E. coli and Salmonella) occasionally caused abortion, disseminated intravascular coagulation, or fever in some animals due to the presence of endotoxin. Using whole-cell inactivated vaccines tended to induce primarily circulating antibody, failing to provide immunity against facultative intracellular or obligate intracellular pathogens, which required the induction of cell-mediated immunity (17 ). In addition, these vaccines often failed, particularly with the gram-negative enteric pathogens— e.g., E. coli—and those bacteria responsible for causing pinkeye in cattle (Moraxella bovis

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  Hugo and Russell's Pharmaceutical Microbiology

  • Brendan F. Gilmore, Stephen P. Denyer, Brendan F. Gilmore, Stephen P. Denyer(Authors)
  • 2023(Publication Date)
  • Wiley-Blackwell

    (Publisher)

  Toxoid Vaccines are preparations derived from the toxins that are secreted by certain species of bacteria. In the manufacture of such vaccines, the toxin is separated from the bacteria and treated chemically to eliminate toxicity without eliminating immunogenicity, a process termed ‘toxoiding’. Toxoids are often subject to variable composition depending on the detoxifying agent and method used, and on whether these processes are applied before or after purification.

  A variety of reagents have been used for toxoiding, but by far the most widely employed and generally successful has been formaldehyde. Under carefully controlled conditions, this reacts preferentially with the amino groups of proteins, although many other functional groups potentially may be affected. Ideally, the toxoided protein will be rendered non‐toxic, but will retain its immunogenicity. The treated toxins are sometimes referred to as formol toxoids.

  Toxoid Vaccines are very effective in the prevention of those diseases such as diphtheria, tetanus, botulism and clostridial infections of farm animals, in which the infecting bacteria produce disease through the toxic effects of secreted proteins which enzymically modify essential cellular components. Many of the clostridial toxins are lytic enzymes with very specific substrates such as neural proteins. Detoxification is also required for the pertussis toxin component of acellular pertussis vaccines.

  Anthrax adsorbed vaccine is not toxoided but relies on the use of culture conditions that favour production of the protective antigen (binding and internalisation factor) rather than the lethal factor (protease) and oedema factor (adenyl cyclase) components of the toxin. Selective adsorption to aluminium hydroxide or phosphate also slows release of residual toxin.

  23.2.1.4 Bacterial Cell Component Vaccines

  Rather than use whole cells, which may contain undesirable and potentially reactogenic components such as lipopolysaccharide endotoxins, a more precise strategy is to prepare vaccines from purified protective components. These are of two main types, proteins and capsular polysaccharides. Often more than one component may be needed to ensure protection against the full range of prevalent serotypes. The potential advantage of such vaccines is that they evoke an immune response only to the component, or components, in the vaccine and thus induce a response that is more specific and effective. At the same time, the amount of unnecessary material in the vaccine is reduced and with it the likelihood of adverse reaction. Vaccines that have been based on one or more capsular polysaccharides include: Hib vaccine; the Neisseria meningitidis

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  Vaccines for Veterinarians E-Book

  • Ian R Tizard, Ian R. Tizard(Authors)
  • 2019(Publication Date)
  • Elsevier

    (Publisher)

  Cl. perfringens act in a similar matter.

  Toxoids are safe and cannot revert to virulence. They cannot spread to other animals. They are very stable and resistant to damage by temperature and light. They generally induce good humoral immunity but not cell-mediated immunity. As with other nonliving vaccines, toxoids are not always highly immunogenic. As a result, multiple doses may be needed to assure immunity. Additionally, an adjuvant, usually an aluminum salt, must be incorporated into the vaccine. Local reactions such as redness, swelling, and induration at the injection site may develop within a few hours. These usually resolve within 72 hours.

  Conventional immunological wisdom would suggest that the use of antibodies against tetanus toxin (tetanus immune globulin) should interfere with the immune response to toxoid and must therefore be avoided. This is not a problem in practice however, and both may be successfully administered simultaneously (at different sites) without problems. This may be because of the relatively small amount of immune globulin usually needed to protect animals.

  Bacterin-toxoids

  Some veterinary vaccines combine both toxoids and killed bacteria in a single dose by the simple expedient of adding formaldehyde to a whole culture. These products, sometimes called anacultures or bacterin-toxoids, are used to vaccinate against Clostridium haemolyticum and Cl. perfringens. Trypsinization of the mixture may make it more immunogenic. Other bacterin-toxoids may have improved efficacy by adding other purified immunogenic antigens. For example, Escherichia coli bacterins against enteric colibacillosis in calves and pigs may be made more effective by the addition of additional fimbrial adhesion proteins such as F4 (K88), F5 (K99), F6, F7, and F18. Antibodies to these antigens prevent Escherichia coli binding to the intestinal wall and thus contribute significantly to protection. Similarly, Mannheimia

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  The Covid-19 Vaccine Guide

  The Quest for Implementation of Safe and Effective Vaccinations

  • Kathryn M. Edwards, Walter A. Orenstein, David S. Stephens(Authors)
  • 2021(Publication Date)
  • Skyhorse

    (Publisher)

  There are many types of vaccines. The first vaccines developed were modeled on those of Jenner and included related viruses or bacteria that infected animals and were able to induce cross-protective immunity against human pathogens, when injected into humans. Examples of these vaccines include the previously mentioned smallpox vaccine used by Jenner and another animal bacteria from cows, called BCG, that is administered to children in developing countries to protect against tuberculosis. Next came killed whole viruses or bacteria with an excellent example being the inactivated or killed polio vaccine (IPV) developed by Jonas Salk, which became available in 1955. Another vaccine in this category includes a virus to prevent hepatitis (inflammation of the liver) called hepatitis A.

  Some bacteria cause disease by excreting potent substances, called toxins, into the body. There are ways to chemically alter these toxins so they no longer cause disease but do stimulate a protective immune response. These are called “toxoids” and the major examples of these are toxoids to prevent tetanus and diphtheria, which are given as part of the combined diphtheria, tetanus, and pertussis (DTP) vaccine. Another example of the use of proteins released from an organism to produce vaccines is the acellular pertussis or whooping cough vaccine, which contains several of these purified proteins from the pathogen (called Bordetella pertussis ) and used as a vaccine.

  A major breakthrough in vaccinology came with the development of live attenuated or weakened pathogens that through repeated passage in the laboratory lost their virulence but maintained their ability to induce a protective immune response. Examples of these vaccines include those against measles, mumps, rubella, varicella (chickenpox), and yellow fever. The organisms in these vaccines can reproduce in the body following administration, cause the immune system to recognize them as foreign, and thereby induce the immune system to make and sustain a protective immune response.

  Some bacteria have capsules made of complex sugars, called polysaccharides, to protect the bacteria. Another class of vaccines induce the immune system to make antibodies against these polysaccharides and protect the body from diseases these bacteria cause. Sometimes these polysaccharides do not induce a protective immune response by themselves, particularly in young children. But when the polysaccharides are chemically linked to proteins, they become better able to stimulate a potent immune response. These are called protein-polysaccharide conjugate vaccines. Examples of such vaccines are the pneumococcal conjugate vaccine, which protects against common causes of severe pneumonia and the meningococcal conjugate vaccines that protect against epidemic meningitis.

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  Treatments from Toxins

  The Therapeutic Potential of Clostridial Neurotoxins

  • Keith Alan Foster, Peter Hambleton, Clifford C. Shone(Authors)
  • 2006(Publication Date)
  • CRC Press

    (Publisher)

  Choosing a nontoxic and functionally inactive fragment of the neurotoxin as a vaccine candidate eliminates the need to grow and handle large quantities of C. botulinum cultures and neuro-toxins and the requirement to perform such activities in dedicated facilities under high biosafety containment levels. Additionally, recombinant vaccines make quality attributes such as identity, purity, and stability more amenable to analysis and characterization both at the genetic and protein levels. Recombinant vaccines developed against the botulinum neurotoxins are safe, potent, and efficacious, and can be reproducibly manufactured with high degrees of consistency from lot to lot. The advances in the field of recombinant botulinum vaccines against all botulinum neurotoxin (BoNT) serotypes will be discussed. 4.2 Toxoid VaccineS 4.2.1 E ARLY T OXOID D EVELOPMENT AND U SE In 1924, Weinberg and Goy 1 first reported the production of a vaccine using formaldehyde treatment of crude extracts derived from neurotoxin-producing Vaccines to Protect against Neurotoxins 77 bacteria, a process known as toxoiding. The immunogenicity of such preparations was confirmed in animals by others. 2–8 Several groups have developed and used Toxoid Vaccines to protect domestic animals from disease. In particular, an effec-tive type C toxoid was prepared for controlling botulism in sheep and cattle in Australia. 9–10 Sterne and Wentzel 11 demonstrated that mass vaccination of cattle with combined types C and D toxoids effectively reduced cattle losses resulting from botulism. Methods for preparing type C toxoid for controlling botulism in domestic minks 12 and game birds 13,14 have also been described. Barron and Reed 15 presented a systematic study of methods for preparing crude alum-precipitated type E toxoid. Crude type E 16–21 and type F toxoids 22 have also been prepared for vaccinating animals and preparing antitoxins.

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  Vaccine Supply and Innovation

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  • 0(Publication Date)
  • The National Academies Press

    (Publisher)

  2 Vaccines: Past, Present, and Future TYPES OF IMMUNIZATION Immunization involves the induction (or administration) of antibodies and other natural defense mechanisms to protect against specific pathogens. There are two types of immunization, active and passive. Active immunization is the major focus of this report. It involves the administration of a modified pathogenic agent, or a component of a pathogen, to stimulate the recipient's immune mechanisms to produce long-lasting protection without causing the clinical manifestations or other consequences of disease. Three major types of preparations are employed to produce active immunity. The first consists of vaccines made from whole, inactivated (killed) pathogens or components of a pathogen. 1 Examples of whole, inactivated vaccines include currently licensed pertussis vaccines, influenza vaccines, and the Salk poliovirus vaccine. The pneumococcal, meningococcal, and hepatitis B vaccines are among those that contain the immunity-producing fraction of the pathogen. Toxoids are the second type of active immunogen. The diphtheria and tetanus vaccines are good examples. Toxoids are toxins that have been treated by physical or chemical means until they no longer produce clinical disease, but retain the capacity to induce immunity. Attenuated infectious vaccines are the third type. Virus vaccines in this group are derived from the offending organism after it has undergone repeated passages in the laboratory in culture; it remains infectious for man but loses the ability to induce clinical disease. Examples include the oral (Sabin) poliovirus vaccine, and the measles, mumps, rubella, and yellow fever vaccines. Other examples of this type of vaccine contain live organisms or agents that are related to but different from the species that causes the disease.

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  Encyclopedia of Pharmaceutical Technology

  Volume 6

  • James Swarbrick(Author)
  • 2013(Publication Date)
  • CRC Press

    (Publisher)

  Unit–Vali dation Vaccines and Other Immunological Products Suresh K. Mittal Harm HogenEsch Department of Veterinary Pathobiology, Purdue University, West Lafayette, Indiana, U.S.A. Kinam Park Departments of Pharmaceutics and Biomedical Engineering, Purdue University, West Lafayette, Indiana, U.S.A. INTRODUCTION The concept of vaccination was introduced in the late 18th century by Edward Jenner when he used cowpox virus as a vaccine to protect humans against smallpox virus infections. This led to the develop-ment of vaccines over the next 2 centuries to provide protection against various bacterial and viral patho-gens. Undoubtedly, the effective vaccination against infectious diseases is the best method of reducing suffering of human and animals caused by viral, bacterial, and parasitic infections. Over the last 200 years, the technology of vaccine development and production has not changed significantly. This usually involves the use of either a killed pathogen combined with an adjuvant or a livepathogen with reduced virulence. Apart from the tremendous suc-cess of killed and attenuated virus vaccines over the years, many of such vaccines do not provide satisfactory protection, and there are a number of other disadvantages associated with these vaccines. Additionally, there are important pathogens against which attempts to develop effective vaccines using traditional approaches were unsuccessful. Various protective viral antigens (envelope and/or capsid proteins or glycoproteins and other viral proteins) and bacterial antigens (surface, internal, or fimbria proteins; bacterial polysaccharides; bacterial toxins; and other proteins involved in bacterial metabolism) have been identified as potential vaccine candidates. These protective antigens are used by various means to develop effective vaccines.

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