Biological Sciences
Inactivated Vaccine
An inactivated vaccine is a type of vaccine that contains viruses or bacteria that have been killed or inactivated so they cannot cause disease. These vaccines stimulate an immune response in the body without causing the actual disease. Inactivated vaccines are often used to protect against diseases such as polio, influenza, and hepatitis A.
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10 Key excerpts on "Inactivated Vaccine"
eBook - PDF- James Swarbrick(Author)
- 2013(Publication Date)
- CRC Press(Publisher)
These protective antigens are used by various means to develop effective vaccines. The field of vaccine technology is not limited to infectious diseases but has shown potential in other areas, such as cancer treatment, reproduction, and modulation of animal productivity. An overview of vaccine strategies is depicted in Fig. 1. Conventional Vaccines Inactivated Vaccines Inactivated (killed) pathogenic organisms can be used in vaccines. This is the simplest way to produce vaccines, provided the organisms can be cultured easily. Therefore, this method is often first tested to develop a potential-vaccine. As with any other technique of vaccine pro-duction, this procedure is only good for some organisms. There are a number of methods of inactivating patho-genic organisms; the most common are treatment with chemicals (formalin, formaldehyde, or propiolactate), heat, or g -irradiation. Insome instances, the procedure of inactivation may enhance antigenicity of some antigens important in protection. Inactivated Vaccines usually result in good humoral immune response after multiple inoculations. Because Inactivated Vaccines in general fail to elicit effective mucosal and cell-mediated immune responses, they may provide limited protection against mucosal and intracellular pathogens. Failure to inactivate the pathogenic organisms completely could result in dis-ease instead of protection. During the 1950s, some lots of poliovirus vaccine were not inactivated completely. [1,2] Now, the methods used to detect residual infectivity are more stringent, therefore, Inactivated Vaccines are con-sidered safe with extremely low or no chance of infection. There have been instances in which inactivated vac-cines led to atypical disease or enhanced disease severity. For example, in the 1960s, formalin-inactivated respira-tory syncytial virus (RSV) vaccine actually enhanced the disease symptoms when vaccinated children were naturally exposed to RSV.
eBook - ePub- Brendan F. Gilmore, Stephen P. Denyer, Brendan F. Gilmore, Stephen P. Denyer(Authors)
- 2023(Publication Date)
- Wiley-Blackwell(Publisher)
Inactivated Vaccines therefore usually have to be relatively concentrated suspensions. In addition, careful control of the culture conditions and the inactivation process is essential to maintain consistency. Even so, such preparations are often rather poorly protective, possibly because of partial destruction of protective antigens during the killing/inactivation process or inadequate expression of these during 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 sensitised (‘primed’) by a previous dose of the same vaccine. The best‐known Inactivated 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, for example, acellular pertussis and typhoid Vi polysaccharide vaccines. 23.2.1.3 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’. 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
- Raj, G Dhinakar(Authors)
- 2018(Publication Date)
- Daya Publishing House(Publisher)
Advantages Broad humoral and CTL responses. Attenuated organism replicates within the host and induces memory. Most vaccines require one exposure. Vaccine can be administered at the normal route of entry, ensuring protection at this site. Vaccines elicit mucosal immune responses. Disadvantages Danger of reversion of attenuated form to virulent form. Attenuated strain could recombine with natural pathogenic strain resulting in new form. Difficult to prepare. Growth culture could be contaminated with other substances. 6.2.2 Inactivated Vaccine Inactivated Vaccines are made by killing or inactivating a pathogen by heat, or chemical means. The inactivation ensures that the pathogen can no longer replicate within the host but would generate immune responses. Advantages Uses pathogen that is killed and no longer capable of replicating within the host. It is easily phagocytosed and presented to Th cells. The full range of antigens is presented ensuring a broad immune response. Since the organism is dead - no disease in host. Vaccine is relatively heat stable. Disadvantages Inactivated Vaccines produce a strong humoral response but weak This ebook is exclusively for this university only. Cannot be resold/distributed. CTL mediated response. No replication in host - presence of antigen is short-lived - requires booster vaccinations. Many pathogens have endotoxins that are not removed - cause serious side effects. Inadequate killing cause disease. 6.2.3 Subunit Vaccines DNA coding for an immunogenic protein of a pathogen can be inserted into either bacteria, yeast, viruses which infect mammalian cells or by transfection of mammalian cells. The cells will then produce the protein endogenously and the protein can be harvested. Large amounts of antigen can be produced inexpensively. Genetic manipulation of antigen possible. Antigens can be made more immunogenic or can be genetically inactivated. Advantages Safe to use on immuno suppressed individuals.
eBook - PDF- Ronald W. Ellis(Author)
- 2001(Publication Date)
- CRC Press(Publisher)
C hapter 8 Inactivated Virus Vaccines Andrew D. Murdin, Benjamin Rovinski, Suryaprakash Sambhara Introduction I nactivated virus vaccines have made a significant contribution to the control of infectious disease during the 2 0 th century and will surely remain an important feature of vaccination strategies in the 21st century. Inactivated Vaccines are currently widely available for polio myelitis, influenza, rabies, hepatitis A, tick-borne encephalitis (TBE) and Japanese encephalitis (JE), and several other products are available for limited, primarily military, use. Inactivated Vaccines have been proposed for several other viruses, most notably H IV (see below), hantaviruses1'4 and dengue,5'7 but are not yet licensed. For comprehensive and up-to-date reviews concerning specific products, the reader is referred to the various chapters of Plotkin and Orensteins definitive work on vaccines.8 In the space available we clearly have to take a selective approach to the subject, so we have divided this chapter into two parts. The first part provides a brief overview of the major inacti vated virus vaccines currendy available, while the second part considers some of the issues presently facing inactivated virus vaccines, with a particular focus on poliovirus, influenza virus and HIV vaccines. We have chosen these vaccines because these can be considered to represent three different stages in the lifecycle of a vaccine. Poliovirus is likely to follow smallpox as the second human pathogen to be successfully eradicated, which influences and limits the way that polio vaccines will be used and developed in the future. Influenza vaccine is a mature and effective product, but one for which there is both scope and demand for improvement. HIV vaccines have been tested in clinical trials but are still very much a developing technology and as such provide an insight into the future of inactivated virus vaccines.
eBook - PDF- (Author)
- 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.
eBook - PDF- Firdos Alam Khan(Author)
- 2014(Publication Date)
- CRC Press(Publisher)
It has been found that cellular vaccines exhibit some similarities to killed vaccines. In addition, neither killed nor acellular vaccines can cause disease in humans and, therefore, are considered to be safe for use in immunocompromised patients. A third way of producing a vaccine is to attenuate or weaken a live microorganism by an aging process or by altering its growth conditions or status. Vaccines that are made with this method are often the most effective vaccines, probably because they multiply in the body by causing a large immune response. Nevertheless, attenuated vaccines also bring the greatest hazard because they can mutate back to the virulent form at any time. Such mutation would result in induction of the disease rather than protection against it and for this reason, attenu-ated vaccines are not recommended for use in immunocompromised patients. Examples of attenuated vaccines are those that protect against mumps, rubella, and measles. 98 Biotechnology in medical sciences Another method of making a vaccine is to use other microorganisms, which are simi-lar to the virulent organism, but that does not pose serious disease. An example of this type of vaccine is the BCG vaccine used to protect against Mycobacterium tuberculosis . The BCG vaccine currently in use is an attenuated strain of Mycobacterium bovis and requires boosters every 3–4 years. In addition, the tools of genetic engineering techniques have been used to produce subunit vaccines, which means only parts of vaccines are used to stimulate a strong immune response. In order to create a subunit vaccine, researchers first isolate the gene or genes that code for appropriate subunits from the genome of the infectious agent. Then, genetic material is placed into bacterial host cells, which produce large quantities of subunit molecules by transcribing and translating the inserted foreign DNA.
eBook - ePubVaccinology
An Essential Guide
- Gregg N. Milligan, Alan D. T. Barrett, Gregg N. Milligan, Alan D. T. Barrett(Authors)
- 2014(Publication Date)
- Wiley-Blackwell(Publisher)
Unfortunately, little was known about the complexities of scale-up or the kinetics of poliovirus inactivation by formalin. When the first Inactivated Vaccines were licensed, all the manufacturers experienced production and quality control problems, culminating in the “Cutter Incident” of cases of paralytic poliomyelitis in 1955, which were caused by residual infectious virus in some of the new vaccine lots, particularly those produced by Cutter Laboratories. This led to the temporary suspension of the polio vaccine programs in the USA and elsewhere. Inactivated Vaccine was subsequently rereleased after additional safety tests demonstrated consistency in production and viral inactivation. As a consequence of the problems with the Salk vaccine, the regulatory functions at the US National Institute of Allergy and Infectious Diseases (part of the National Institutes of Health) were moved to a separate institute, the Division of Biologics Standards, ultimately becoming the modern Center for Biologics Evaluation and Research of the Food and Drug Administration.In the 1950s, Albert Sabin in Cincinnati and investigators at a number of other laboratories took the three strains of polioviruses (one each for the three serotypes of poliovirus) and passaged them repeatedly in monkey tissue cultures, testing them for attenuation by inoculating monkeys. The least neurovirulent of these, the Sabin vaccine candidate, was ultimately selected. Sabin field tested his oral vaccine in 75 million people in the former Soviet Union.Immunologically, the Inactivated Vaccine differs substantially from the attenuated vaccine in that Inactivated Vaccine only induces humoral immunity whereas the live virus vaccine induces both humoral and duodenal antibodies (see Figure 1.6 ).Figure 1.6 Serum and secretory antibody responses to orally administered, live attenuated polio vaccine and to intramuscular inoculation of inactivated polio vaccine. From Ogra PL, Fishant M, Gallagher MR (1980). Viral vaccination via mucosal routes. Review of Infectious Diseases 2(3); 352–369.In the 1960s, an adventious virus, simian virus 40 (SV40), which has been shown to cause tumors in rodents and can transform human tissue culture cells, was recognized in primary monkey kidney tissue cultures used to prepare some vaccines. It is estimated that up to 100 million Americans may have been exposed to SV40, which contaminated the inactivated polio vaccine when it was first introduced. In addition, SV40 also contaminated the first oral polio vaccine, but that contaminated vaccine was only given to people during the original clinical trials. Furthermore, SV40 has been found as a contaminant of some of the adenovirus vaccines given to military recruits during that same period of time. Once the contamination was recognized, steps were taken to eliminate it from future vaccines; no vaccines licensed for use in the USA or other countries currently are contaminated with SV40.
eBook - PDF- Rebecca Richards-Kortum(Author)
- 2009(Publication Date)
- Cambridge University Press(Publisher)
The immune system treats live, attenuated vaccines in just the same way as it would an infectious pathogen. Thus, these vac-cines stimulate both humoral and cell-mediated immu-nity. As a result, they usually provide lifelong immunity. However, such vaccinations can produce disease in an immunocompromised host [ 5 ]. A technical challenge of this approach is that it is not always feasible to produce strains of a pathogen that have been attenuated suffi-ciently. In addition with pathogens that undergo anti-genic drift, there is a finite risk of reversion to a virulent form [ 14 ]. Vaccines based on live attenuated pathogens account for approximately 10% of total vaccine sales [ 15 ]. Subunit vaccines Our immune system generally recognizes and responds to a portion of an infectious organism known as an anti-gen. If we can identify the antigen that will produce an immune response, we can purify that antigen and use it as the basis for a vaccine. This type of vaccine is very safe because there is no risk that it can lead to infection, even in an immunocompromised host [ 5 ]. Several strategies have been developed to produce sub-unit vaccines. For example, many bacteria produce dis-ease by secreting toxins that interfere with normal cell function. We can create an immune response to these toxins by vaccinating with purified bacterial toxins that have been chemically treated to make them harmless. This type of vaccine is known as a toxoid vaccine and it produces an immune response without symptoms of disease [ 14 ]. The diphtheria and tetanus vaccines are examples of toxoid vaccines [ 5 ]. Alternatively, a subunit vaccine can use part of a pathogen to induce an immune response but not disease. Our immune system responds to the polysaccharides found on the surface of certain bacteria. We can grow bacteria in culture and extract these polysaccharides from the culture media the bacte-ria are grown in to develop a vaccine.
eBook - PDF- Neil J. Salkind(Author)
- 2005(Publication Date)
- SAGE Publications, Inc(Publisher)
VACCINATION Vaccination is a process that artificially confers immunity to an individual against a specific type of disease caused by infectious microorganisms (viruses, bacteria, fungi, or parasites). Vaccines work by using the body’s ability to remember previous infections. When an individual becomes infected by an infectious organism for the first time, the immune system recog-nizes and then destroys it by mounting an immune response specific for that organism. Upon an individ-ual’s second exposure to the same microorganism, the immune system recognizes and eliminates it by mounting immune responses that occur more rapidly and are greater in magnitude than those induced on the first encounter. Thus, the infection will not develop to a severe level or to the disease stage. This ability to remember infections, called immune mem-ory , allows people to become immune to a disease after they have caught it once. A vaccine simulates that first infection by exposing an individual to a par-ticular microorganism or portions of that microorgan-ism without causing infection and illness. There are several disease-causing microbes for which vaccines exist. Thus, these diseases can be prevented. Some of the most common vaccine-preventable diseases are diphtheria, tetanus, pertussis, some forms of bacterial meningitis, pneumococcal pneumonia, measles, mumps, rubella, chickenpox, influenza, hepatitis A, hepatitis B, poliomyelitis, and rabies. However, there are still many diseases for which effective vaccines are not available. Some of these diseases are the acquired immunodeficiency syndrome (AIDS), malaria, and schistosomiasis. Vaccines are made from either all or portions of the microorganism against which the vaccine protects. These portions of the microorganisms are called anti-gens and, in most cases, are proteins, glycoproteins, or polysaccharides.
eBook - PDF- Frederick A. Murphy, E. Paul J. Gibbs, Marian C. Horzinek, Michael J. Studdert(Authors)
- 1999(Publication Date)
- Academic Press(Publisher)
Unfortunately, even vaccines con- taining more than one ts mutation have displayed a dis- turbing tendency to revert toward virulence during replication in vaccinated animals. Attention accordingly moved to cold-adapted (ca) mutants, derived by adapta- tion of virus to grow at suboptimal temperatures. The rationale is that such mutant viruses might comprise safer vaccines for intranasal administration in that they would replicate well at the lower temperature of the nasal cavity (about 33~ in most mammalian species), but not at the temperature of the more vulnerable lower respiratory tree and lungs. Cold-adapted influenza vac- cines containing mutations in almost every gene do not revert to virulence. In 1997, influenza vaccines based on such mutations were licensed for human use in the United Statesmthe same approach is currently under study for the development of improved vaccines against equine in- fluenza. Nonreplicating Native Antigen Vaccines Vaccines Produced from Inactivated Whole Virions Inactivated virus vaccines are usually made from virulent virus; chemical or physical agents are used to destroy infectivity while maintaining immunogenicity. When prepared properly, such vaccines are safe, but they need to contain large amounts of antigen to elicit an antibody 228 13. Vaccination against Viral Diseases response commensurate with that attainable by a much smaller dose of attenuated virus vaccines. Normally the primary vaccination course comprises two or three injec- tions; further (booster) doses may be required at inter- vals to maintain immunity. The most commonly used inactivating agents are formaldehyde,/~-propiolactone, and ethylenimine. One of the advantages of/3-propiolactone, which is used in the manufacture of rabies vaccines, and ethylenimine, which is used in the manufacture of foot-and-mouth disease vaccines, is that they are completely hydrolyzed within hours to nontoxic products.
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