The effect of peptic digestion on the properties of diphtheria antitoxin

Abstract

Diphtheria antitoxin prepared in the horse and refined by peptic digestion when injected in very large doses into women in an advanced stage of pregnancy did not pass to the infant. In pregnant guinea-pigs diphtheria antitoxin (naturalserum, ex -guinea-pig) passed to the young in abundance; but, after peptic-digestion, this homologous antitoxin failed entirely to pass the placenta, the young being devoid of antitoxin at birth. The passage was not affected by the treatment of the natural serum with ammonium sulphate as used in the Gibson-Banzhaf (1910) process for the concentration of antitoxin. Diphtheria antitoxin (natural serum ex -horse) passed from pregnant guinea-pigs to their off spring in smaller amounts and much less readily than homologous antitoxin, and the quantity of antitoxin( ex -horse) so passing was reduced even further and very considerably as a result of peptic digestion. Even under the most favourable conditions homologous antitoxin takes sometime (2 or 3 days) to attain the same concentration in the young as in the mother; but once this concentration has been attained it is preserve data high level for long periods. Passive anaphylactics ensitization of guinea-pigs, either of the whole animal or the isolated uterus, is easily effected, in vivo or in vitro , by small quantities of diphtheria antitoxin (either natural serum or ammonium sulphate concentrated, ex -guinea-pig), but this property is completely lost when the homologous antitoxin is subjected to peptic digestion. It is not possible to sensitize anaphylactically guinea-pigs, in vivo or in vitro , by means of diphtheria antitoxin, ex -horse, whether the antibody is presented either in the form of natural serum, or concentrated by means of ammonium sulphate; and the result is the same when pepsin-refined diphtheria antitoxin ex -horse is used. When 5 or 10 units of diphtheria antitoxin ex -horse, whether as natural serum, ammonium-sulphate concentrated or pepsin-refined, are injected subcutaneously into guinea-pigs, the animals are rendered Schick-negative in a few hours. These antitoxins are eliminated in about a week, after which time the injected guinea-pigs are found to be Schick-positive again. If, however, the same amounts of antitoxin made in guinea-pigs are injected into guinea-pigs the result is different; the animals also become Schick-negative, but this condition is maintained for a month or longer. That is, homologous antitoxin is eliminated much more slowly; but if this natural serum antitoxin from the guinea-pig is subjected to peptic digestion it is eliminated as quickly as diphtheria antitoxin made in the horse. When diphtheria toxin is injected intracutaneously into guinea-pigs, a quantity of diphtheria antitoxin 50,000 times as large as that required to neutralize it in vitro is required for neutralization in the animal, and then only if injected intravenously within 1hr.; but little or no neutralization in vivo occurs if the intravenous injection is longer delayed, whatever type of homologous or heterologous antitoxin is administered.