United States standard diphtheria toxin for the Schick text and the erythema potency assay for the Schick text dose.

A diphtheria toxin shown to have high toxicity and avidity and to combine with antitoxin in multiple proportions was selected for the U.S. standard diphtheria toxin for the Schick test and freeze-dried. Assayed values per vial were 1.09 L(f), 1.09 L(r), 1,090 Schick test doses (STD), 33 LD(80), 38 LD(50), and 43,000 minimum skin reactive doses. One STD (L(r)/1000) is slightly more toxic than one unit of the international standard (L(f)/1,000). Experiments showed that the potency assay of Schick test toxin by guinea pig erythema toxicity, determined relative to the toxicity of the standard, was highly reproducible and significantly more reproducible than the lethal (minimum lethal dose) test and that the STD, defined as one L(r)/1000, was equivalent to approximately 1/50 minimum lethal dose. The erythema potency assay was prescribed in the U.S. standards for Schick test toxin effective in 1969.

Immunization against neonatal tetanus in New Guinea. 5. Laboratory assayed potency of tetanus toxoids and relationship to human antitoxin response.

Previous papers in this series have shown that plain toxoids induced early primary antitoxin levels in women in New Guinea that were not significantly different from those induced by adsorbed toxoids but that at the end of 1 year the antitoxin levels differed significantly. Protective levels (not less than 0.01 unit/ml) induced by adsorbed toxoids persisted for more than 3 years. Results of laboratory assays of the toxoids reported in this paper show that per total human immunizing dose, the plain toxoids had 72 or less international units (IU) whereas the adsorbed toxoids had approximately 200 IU. The international "unitage" of these toxoids reflected the persistence of the human protective antitoxin level but not the early primary response. The assay results were in agreement with findings of other workers that the mouse as well as the guinea-pig may be satisfactory for potency assay of adsorbed toxoids. The need for determination of the international unitage of tetanus toxoids used in human studies and the confirmation of relationship of this value to persistence of antitoxin levels is emphasized.

Comparison of titrations on the chorioallantoic membrane of chick embryos with the rabbit scarification technique for the potency assay of smallpox vaccines.

The potency of the U.S. Reference Smallpox Vaccine, Lot 2, the International Reference Preparation of Smallpox Vaccine, and commercial smallpox vaccines was determined by the chorioallantoic membrane (CAM) and rabbit scarification (RS) potency assay methods. The mean titer of the U.S. Reference (based on 107 ampoules) was 10(8.1) pock-forming units (PFU) per ml and that of the International Reference (based on 3 ampoules) was 10(7.8) PFU/ml. A statistical analysis of the CAM data for the U.S. Reference resulted in the establishment of a table of limits of acceptance for smallpox vaccines. Of the commercial smallpox vaccines tested by the CAM and RS methods, 89% demonstrated potencies comparable to the U.S. Reference. Our results show that the CAM test method has application in the control testing of smallpox vaccines produced by U.S. licensed manufacturers provided it is used within the limits discussed.