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This modified toxin was suitable for immunizing
animals to obtain antitoxin but was found to cause severe local reactions in
humans and could not be used as a vaccine.
In 1909, Theobald Smith, in the U.S., demonstrated that diphtheria toxin
neutralized by antitoxin (forming a Toxin-Anti-Toxin complex, TAT) remained
immunogenic and eliminated local reactions seen in the modified toxin...
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For some
years, beginning about 1910, TAT was used for active immunization against
diphtheria. TAT had two undesirable characteristics as a vaccine. First, the
toxin used was highly toxic, and the quantity injected could result in a fatal
toxemia unless the toxin was fully neutralized by antitoxin...
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