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Live natural virulent vaccination

Maximum protection is best achieved using live organisms as antigen, though there are obvious risks. Despite this, and in the absence of any safer alternative, in the Middle East parents often expose the buttocks of their children to sandfly holes, ensuring infection with cutaneous Leishmania species (an organism carried by sandfly vectors). Infection is self-limited and provides long-lived sterile immunity (without the risk of scarring on visible body areas, as occurs following natural infection).

Fig. 12.4. Adjuvants used in vaccines. Adjuvants enhance the immune response when administered as components of a vaccine. Most common in human vaccines are inorganic salts (based on aluminum hydroxide (alum) or calcium phosphate). Both act primarily to produce a depot effect. Immune stimulating complexes (ISCOMs) have been introduced to produce essentially the same effect, by incorporating the antigen within a liposomal particle that is presented to APC. Less commonly used adjuvants are products of bacterial cells e.g., Bordetella pertussis, (used with tetanus and diphtheria toxoids), which act to stimulate local cytokine production.

Adjuvants are used to

Enhance the immune system and include

Calcium

Inorganic salts Immune stimulating complexes that include that consist of

Liposomes plus antigen that produce a phosphate Aluminunli hydroxide Depot effect that produce a Depot effect

Bacterial cell products such as

Bordetella Pertussis ( inactivated) that stimulate Cytokine production when used with

Toxoids (Tetanus and Uiptheria)

Attenuated vaccines

Generating attenuated organisms

Attenuated organisms are avirulent but maintain the antigenic epitopes of virulent strains. This is frequently achieved by modifying the culture conditions in which the organisms grow, as was the case for the first successful application of this technology, by Calmette and Guerin. They passaged a bovine strain of Mycobacterium tuberculosis in culture to produce the less virulent Bacillus Calmette Guerin (BCG), which provides some protection against human tuberculosis. Greater success was achieved for virally induced disorders, where live attenuated viral vaccines decreased the incidence of measles, mumps, rubella and poliomyelitis well over 100-fold.

Attenuated organisms and reversion to wild type

Attenuated organisms harbor the risk of reversion to virulence (e.g., for types 2 and 3 poliomyelitis virus). In Sweden this led to the withdrawal of the live attenuated polio vaccine from routine use). Molecular biological investigations help us understand these cases. An attenuated form is produced in culture after accumulation of mutations at random which, while preserving antigenicity, decrease virulence. For the type 1 polio vaccine (which has never reverted), over 50 mutations exist in the attenuated form, while for types 2/3 only two important mutations occurred to produce the attenuated forms-thus their reversion rates were much higher. Using molecular tools to introduce multiple mutations (site-directed mutagenesis) live attenuated vaccines may be produced in future which have low risks of reversion.

Attenuated viruses commonly used

Two live attenuated viral vaccines commonly used in North America/Europe are the Sabin polio vaccine and a measles vaccine. Because the natural route of polio infection is the gastrointestinal tract, the Sabin vaccine is generally administered orally to protect individuals against a disease that causes paralysis and death. Children receive Sabin poliovirus vaccine at two, four, and six months of age, with a booster dose administered just before school entry. Measles vaccine is also a live attenuated virus, which protects individuals from an infectious disease that may be accompanied by pneumonia or encephalitis. Children are generally vaccinated at twelve months, with a booster injection given just before school entry.

Inactivated (killed) organisms

Inactivated or killed viruses and bacteria are also used in vaccines. They are generally safer, but less effective. The Salk polio vaccine, used in Scandinavia following problems with the attenuated Sabin vaccine, is an inactivated poliovirus vaccine for intramuscular injection. Less effective than the Sabin vaccine, it is safer and can be used in immunocompromised individuals. Rabies virus vaccine is also reasonably efficacious. Killed organisms in cholera (bacteria) and influenza (virus) vaccines are only moderately effective for vaccine purposes. Even killed

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