Studies on Immunity to Toxins of Clostridium Botulinum

Summary

The response of man to immunization with a purified, bivalent, AB botulinum toxoid was investigated. The toxoid was well tolerated; only occasional mild local reactions were encountered. Four schedules of immunization were studied; 0.5-ml injections were given at 0, 2, 4 and 6 weeks, at 0 and 8 weeks, at 0, 2 and 10 weeks and at 0 and 10 weeks; serum antitoxin titers were determined at intervals thereafter. Titers of 0.02 unit of type A and 0.005 unit of type B antitoxin were considered satisfactory, since guinea pigs with these antitoxin levels survived intraperitoneal i.p. challenge with approximately 10⁵ mouse i.p. LD₅₀ of homologous toxin. The 0-2-10 week immunization schedule produced the highest proportion of satisfactory titers, and the highest mean titers. Booster inoculations of 0.5 ml were given 1 year after the initial injection, except for one group in which boosters were given after 6 months. Marked increases in antitoxin titers were observed following the 1-year boosters, the mean titers reaching a value at least 500 times the satisfactory level and remaining well above this level for at least 2 years. Six-month boosters were considerably less effective, both with respect to the magnitude and to the duration of the secondary response. Prior immunization with univalent type A toxoid depressed the response to the type B component of the bivalent preparation. After storage for 3¼ years at 4°C the toxoid appeared to have deteriorated slightly, although considerable antigenicity remained.