Vaccines inactivated pathogen

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... 

Table 13.8 Some vaccine preparations that consist not of intact attenuated/ inactivated pathogen, but of surface antigens derived from such pathogens...

Heat is the most reliable method of virus disinfection. Most human pathogenic viruses are inactivated following exposure at 60°C for 30 minutes. The virus of serum hepatitis can, however, survive this temperature for up to 4 hours. Viruses are stable at low temperatures and are routinely stored at -40 to -70°C. Some viruses are rapidly inactivated by drying, others survive well in a desiccated state. Ultraviolet light inactivates viruses by damaging their nucleic acid and has been used to prepare viral vaccines. These facts must be taken into account in the storage and preparation of viral vaccines (Chapter 15). 

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. 

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

Vaccines are derived from whole or fragments of pathogens, either through inactivation or attenuation of the pathogen or by generating the... 

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... 

Modem subunit vaccines contain one or more selected antigenic subunits that have been found to provide protection against a particular pathogen. They are better defined from a physicochemical aspect and have fewer side effects than vaccines, which contain intact cells, whether inactivated or attenuated. Current subunit antigens include viral and bacterial proteins as well as bacterial capsular polysaccharides. 

The future importance of peptide vaccines lies in the fact that one could replace inactivated or attenuated microbial pathogens or toxins, which are high-molecular and therefore difficult to characterize and standardize, by highly specific synthetic peptides. Emini et al.157 have synthesized oligopeptides that prime the rabbit immune system and are effective against poliovirus. The amino acid sequence of the peptide vaccines 63 and 64 originate in the poliovirus VPt protein. 

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. 

There have already been accusations that two patients with AIDS, treated with an experimental vaccine prepared using a Vaccinia virus that had apparently been inactivated and genetically engineered to express HIV proteins, may have died from vaccinia gangrenosa (14,15). On the other hand, there is evidence that recombinant Vaccinia viruses have reduced pathogenicity (SEDA-13, 289). 

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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