Active Immunization of Human Beings with Tetanus Toxoid

Abstract

Apparently the first attempt at active immunization of man was made by Louis Bazy working with Vallee. He gave iodized tetanus toxin obtained from Ramon at the Pasteur Institute to wounded soldiers. Three injections were given 5 days apart and 10 days after the last injection the men were bled and 1 cc. of the serum of each individual examined at the Pasteur Institute was found to contain from 10 to 100 “units” of tetanus antitoxin. In 1927 Ramon and Zoeller used tetanus anatoxin, toxin treated with formaldehyde, and then incubated. They injected several hundred subjects. The greatest immunity was obtained by giving 0.5 cc. of anatoxin, 1 month later 1 cc. and 2 weeks later 1.5 cc. The immunity acquired was apparently so great that 1 cc. of the subject's serum neutralized 500 to 1,000 minimum lethal doses for a guinea pig. Twelve to 18 months later the immunity was still higher. After 1 to 2 years a single injection of anatoxin, the so-called “injection de rappel”, resulted in a great increase in antitoxic power of the serum. 1 cc. of the serum neutralized 10,000 minimum lethal doses. The process of active immunization can not be hurried by shorter intervals between injections or large doses of anatoxin. In May, 1930, we assembled 18 volunteers, 5 adults 18 years and over, and the rest children varying from 5 years up, who were bled and no trace of tetanus antitoxin found in their blood sera. At weekly intervals 3 doses of tetanus toxoid, made by treating the toxin with 0.4% formalin and incubating at 38° for 10 days, were injected intramuscularly. The injections were painful for about 5 minutes, but no general reactions occurred and no local ones beyond moderately sore arms.