Bacteria live attenuated

There are two classical strategies for vaccination. One involves vaccination with either killed pathogenic organisms or subunits of the pathogenic organism. The other utilizes live attenuated viruses or bacteria that do not cause disease but have been derived from the pathogenic parent organism. 

Live, attenuated bacteria, e.g. Bacillus Calmette-Guerin (BCG) used to immunize against tuberculosis. 

If PPD is used as the carrier for peptide immunizations, the animals must first be primed with live attenuated tubercle bacteria (BCG strain), which express PPD on their surface This priming step elicits a strong T-cell helper response against subsequent PPD-linked immunogens. FCA actually appears to interfere with this priming process and so must be avoided if using this method. 

The purpose of this chapter is to review and discuss the preclinical safety evaluation strategy for vaccine approaches to the prophylaxis and treatment of viral diseases. This chapter will discuss the newer approaches to vaccination and will include recombinant proteins, peptides, polysaccharides, DNA plasmids, and viral vectors with and without adjuvants. It is outside the scope of this chapter to discuss whole cells expressing immunogens, live attenuated viruses, bacteria, or parasites. 

Live Attenuated Organisms. Live attenuated bacteria and viruses have been used not only as vaccines but also as a delivery system that elicits humoral, mucosal, and cellular immune responses against exogenous antigens. Since the success with live attenuated oral vaccines against tuberculosis and polio more than 3 decades ago, a number of live attenuated microorganisms have been used as antigen-delivery systems. Live vaccines are relatively easy and cheap to manufacture, because they do not require purification of... 

The harvest is a very complex mixture of bacterial cells, metabolic products and exhausted medium. In the case of a live attenuated vaccine it should be innocuous, and all that is necessary is for the bacteria to be separated and resuspended under aseptic conditions in an appropriate diluent, possibly for freeze-drying. In a vaccine made from a virulent strain of pathogen the harvest may be intensely dangerous and great care is necessary in the subsequent processing. Adequate containment will be required and for class 3 pathogens such as Salmonella typhi or Yersinia pestis or bulk production of bacterial toxins, dedicated facilities that will provide complete protection for the operators and the environment are essential. 

Vaccines also may be used to boost specific immune processes directed against the bacteria themselves or against adherence appendages, cytotoxins, or enterotoxins. Currently available vaccines for typhoid fever in the United States are the parenteral Vi capsular polysaccharide vaccine, the oral live-attenuated Ty21a vaccine, and the older heat-phenol-inactivated parenteral vaccine. Only the older parenteral cholera vaccine is licensed for use in the United States, but it is not recommended owing to the low risk of cholera to the traveler and the limited efficacy of the vaccine. New oral five and killed vaccines are licensed outside the United States and are used by some travelers. The rotavirus vaccine, although effective, has presented complications in the form of rare cases of intussusceptions it is no longer marketed and thus is not recommended. ... 

Vaccine A preparation of whole or parts of living, attenuated, or killed bacteria or viruses, (or synthesized antigens identical or similar to those found in the disease-causing organisms) designed to produce or increase immunity to a particular disease. 

For live attenuated vaccines, specific safety aspects must also be studied clinically. As live viruses or bacteria replicate in the vaccine and may be shed into the environment, the potential transmission of vaccine microorganisms to unvaccinated subjects must be studied. If transmission is possible or Kkely, the vaccine s genotypic and phenotypic stability must be carefully studied and confirmed. 

Traditional vaccines mainly composed of live attenuated or inactivated whole bacteria or viruses, often show unwanted side effects. New generations of vaccines will probably be composed of relevant antigen subunits derived either from the pathogen itself or prepared via molecular, biological or chemical techniques. However, formulations based on antigens or subunits bearing one or more B and T cell epitopes in a monomeric form are often weakly immunogenic when compared to traditional... 

A Soviet-made, live attenuated (non-encapsulated) strain of anthrax, administered in 1943, is probably the first recorded anthrax vaccine made for humans. At about the same time, one of the first orders of business in the United States biological warfare program was also the development of anthrax vaccine. In one of the first efforts, 205 personnel were administered a vaccine made of killed Bacillus anthracis bacteria (the causative agent of anthrax) vaccine. After several months of study, however, it became clear that this vaccine showed little efficacy and was discontinued. 

Live vaccines are normally weakened strains that do not cause diseases in the host, but stiU can stimulate the immune response. A typical example is the poho vaccine. The weakening of microorganisms or attenuation of the vims or bacteria can be accompHshed by passage through different substrates and/or at different temperatures. Modem genetic engineering techniques can also be used to attenuate a vims or bacterium. 

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,... 

It was not until the late 1960 s that encouraging experimental and clinical results were obtained from the treatment of tumors with bacterial preparations other than endotoxins, primarily with an attenuated antituberculosis vaccine consisting of living bacteria of Mycobacterium bovis strain BCG alone or admixed with tumor cells. However, the use of viable cells of BCG caused complications. 

A range of different vaccine vectors has been developed over time to provoke an immune response within the body [127,142], However, it has only been comparatively recently that they have been applied to inducing mucosal immunity within the uterovaginal tract. The general vector platforms that have been used include attenuated viruses, live viruses, commensal bacteria, DNA vectors, and protein subunit/peptide or virus-like particles (Table 21.9). The choice of vector is dependent on a number of factors such as the pathogenic virus and bacterial type and the length of duration of immunity required. 

Louis Pasteur demonstrates that lactic acid fermentation is caused by a living organism. Between 1857 and 1880, he performs a series of experiments that refute the doctrine of spontaneous generation. He also introduces vaccines for fowl cholera, anthrax, and rabies, based on attenuated strains of viruses and bacteria. 

Lugowski, C., Niedziela, T., Jachymek, W. Anti-endotoxin antibodies directed against Escherichia coli Rl oligosaccharide core-tetanus toxoid conjugate bind to smooth live bacteria and smooth lipopolysaccharides and attenuate their tumor necrosis factor stimulating activity, FEMS Immunol Med Microbiol 16 (1996b) 31-38. 

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