Abstract
The earliest bacterial vaccines were live strains derived from virulent cultures isolated from cases of natural infection. These were attenuated by empirical methods based on sub-culture under adverse conditions. Sometimes this involved exposure to unusually high temperatures or culture on media that contained substances inhibitory to wild-type strains. Occasionally attempts were made to select strains by passage in unnatural host species, but generally this approach was less successful than for viral attenuation. Examples of vaccines produced by these processes include the fowl cholera (Pasteurella multocida) and anthrax vaccines developed by PASTEUR (1880, and PASTEUR et al. 1881) and the bacille Calmette-Guérin (BCG) tuberculosis vaccine developed by CALMETTE et al. (1928). The Pasteur anthrax vaccine strains were selected by growth at high temperature (42°C) and were notoriously unstable and difficult to administer consistently.
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Schild, G., Corbel, M., Corran, P., Minor, P. (1999). Vaccines: Past, Present and Future. In: Perlmann, P., Wigzell, H. (eds) Vaccines. Handbook of Experimental Pharmacology, vol 133. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-59955-2_1
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