Killed/inactivated vaccines

Poliomyelitis. Two vaccines are Hcensed for the control of poliomyelitis in the United States. The Hve, attenuated oral polio vims (OPV) vaccine can be used for the immunization of normal children. The killed or inactivated vaccine is recommended for immunization of adults at increased... 

Viral vaccines present problems of safety testing far more complex than those experienced with bacterial vaccines. With killed viral vaccines the potential hazards are those due to incomplete virus inactivation and the consequent presence of residual live virus in the preparation. The tests used to detect such live virus consist of the inoculation of susceptible tissue cultures and of susceptible animals. The cultures are examined for cytopathic effects and the animals for symptoms of disease and histological evidence of infection at autopsy. This test is of particular importance in inactivated poliomyelitis vaccine, the vaccine being injected intraspinally into monkeys. At autopsy, sections of brain and spinal cord are examined microscopically for the histological lesions indicative of proliferating poliovirus. 

There are two basic types of vaccines live (live-attenuated) and killed (inactivated). 

A vaccine consists of a suspension of live (attenuated) or killed (inactivated) microorganisms (in whole or fractions), whereas a toxoid is a detoxified bacterial toxin that has the ability to trigger the production of antitoxin once administered into the body. 

Killed or Inactivated Vaccines Chemical and temperature treatment are normally used to kill or inactivate the pathogen. Formaldehyde treatment is one of the more common methods. Other chemicals used are phenol and acetone. Another method is to irradiate the pathogen to render it inactive. 

Examples of killed or inactivated vaccines are cholera vaccine containing dead strains of Vibrio cholerae, hepatitis A vaccine with inactivated hepatitis A virus, pertussis vaccine with killed strains of Bordetella pertussis, typhoid vaccine with killed Salmonella typhi, and influenza vaccine with various strains of inactivated influenza viruses (see Exhibit 4.2 for a discussion of influenza viruses and vaccines and Exhibit 4.3 on avian influenza H5N1). 

Toxoids Toxoids are derived from the toxins secreted by a pathogen. The advantages and disadvantages are similar to those for killed or inactivated vaccines. 

Another approach is the whole-killed or inactivated vaccine. These vaccines are derived from the pathogen itself, rather than a weakened form, as are live attenuated vaccines. Chemical (e.g., formalin, ether, and beta-propiolactone) or physical (e.g., heat, ultraviolet, and gamma irradiation) means, or combinations thereof, are used to inactivate the pathogen. Notable examples of this type of viral vaccine include the inactivated polio vaccine... 

Very often whole-killed vaccines are formulated with adjuvants, which are designed to enhance vaccine persistence and induction of immune responses. However, the only adjuvant currently approved by FDA for clinical use is alum, in the form of vaccines complexed with aluminum hydroxide or aluminum sulfate. Even with the help of alum adjuvants, inactivated vaccine antigens are presented to APC extracellularly, as opposed to intracellularly, leading to a bias toward antibody-mediated responses. Little or no cell-mediated response to whole-killed vaccines with alum adjuvant renders some vaccines ineffective. 

Several clinical studies have been conducted with oral influenza vaccines (Avtushenko et al. 1996 Lazzell et al. 1984). These include water in oil emulsion form of inactivated virus vaccine and an enteric-coated killed virus vaccine. Although these vaccines induced IgA responses, there were inadequate levels of virus-neutralizing IgG antibodies in the serum to fulfil regulatory requirements for vaccine immunogenicity. This warrants refinement and further development of these types of vaccines. 

Killed or inactivated vaccines contain dead cells of the bacteria or vims that causes the disease to be prevented. Examples include the Salk polio vaccine and the pertussis vaccine. 

Examples of killed or inactivated vaccines are cholera vaccine containing... 

Active immunization, vaccination, involves administration of an antigen as a whole, killed organism, an attenuated (live) organism, or a specific protein or peptide constituent of an organism. Booster doses often are required, especially when killed (inactivated) organisms are used as the immunogen. In the United States, vaccination has sharply curtailed or practically eliminated a variety of major infections, including diphtheria, measles, mumps, pertussis, rubella, tetanus, Haemophilus influenzae type b, and pneumococcus. 

Erna Nemdy. In reading about development of the hepatitis B vaccine, ] Ema Nemdy learned that the first vaccine available for HBV, marketed in 1982, was a purified and inactivated vaccine containing HBV virus that had been chemically killed. The virus was derived from the blood of known HBV carriers. Later, attenuated vaccines were used in which the virus remained live but was altered so that it no longer multiplied in the inoculated host. Both the inactivated and the attenuated vaccines are potentially dangerous because they can be contaminated with live infectious HBV. 

Vaccines can be roughly categorized into killed vaccines and Hve vaccines. A killed vaccine can be (/) an inactivated, whole microorganism such as pertussis, (2) an inactivated toxin, called toxoid, such as diphtheria toxoid, or (J) one or more components of the microorganism commonly referred to as subunit vaccines. The examples are capsular polysaccharide of Streptococcus pneumoniae and the surface antigen protein for Hepatitis B vims vaccine. 

Polio is the only disease, at present, for which both hve and killed vaccines compete. Since the introduction of the killed vims (Salk) in 1956 and the live attenuated virus (Sabin) in 1962 there has been a remaikable decline in the incidence of poliomyelitis (Fig. 16.1). The inactivated polio vaccine (TPV) contains formalin-killed poliovirus of all three serotypes. On injection, the vaccine stimulates the production of antibodies of the IgM and IgG class which neutrahze the vims in the second stage of infection. A course of three injections at monthly intervals produces long-lasting immunity to all three poliovirus types. 

Vaccination to induce an adaptive immune response is expected for a broad range of infectious diseases and cancers. Traditional vaccines are mainly composed of live attenuated viruses, whole inactivated pathogens, or inactivated bacterial toxins. In general, these approaches have been successful for developing vaccines that can induce an immune response based on antigen-specific antibody and cytotoxic T lymphocyte (CTL) responses, which kill host cells infected with intracellular organisms (Fig. 1) [1,2], One of the most important current issues in vaccinology is the need for new adjuvants (immunostimulants) and delivery systems. Many of the vaccines currently in development are based on purified subunits, recombinant... 

Vaccine A preparation of killed or weakened infective or toxic agent used as an inoculation to produce active artificial immunity that is, a suspension of live (usually attenutated) or inactivated microorganisms (e.g., bacteria, virus, or rickettsiae) administered to induce immunity and prevent infectious disease. 

Processing steps after harvesting may be carried out simultaneously in the same production area provided that adequate precautions are taken to prevent cross-contamination. For killed vaccines and toxoids, such parallel processing should only be performed after inactivation of the culture or after detoxification. 

It is an immunobiological substance for producing specific protection against a given disease. It stimulates the production of protective antibodies and other immune mechanisms. Vaccines may be prepared from attenuated live organisms, inactivated or killed microorganisms, toxoids or combination of these and more recent one are recombinant vaccines. 

For many years the preferred approach to immunity to infectious disease lias been by development of active immunity through the injection of a vaccine. The vaccine may be either an attenuated live infections agent, or an inactivated or killed product. In either case, protective substances called antibodies are generated in the bloodstream these, are described in the next section. Vaccines for a number of diseases have been available for many years and have assisted in the eradication of some diseases, such as smallpox. As new strains of bacteria and viruses are discovered, additional vaccines becomes available from time to time. See also Vaccine Technology,... 

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