98 



Scientific Proceedings (33). 



48 (386) 



Toxin-antitoxin mixtures as immunizing agents. 



By WILLIAM H. PARK and EUGENE FAMULENER. 



\_From the Research Laboratory of the Department of Health, New 



York Citj'.] 



Ehrlich early suggested that injections of partially neutralized 

 diphtheria toxin produced activ^e immunity. This was demon- 

 strated by Wernicke, Dreyer and Madsen, Morgenroth, ourselves 

 and others. Smith in a recent article suggested the use of such 

 mixtures in the immunization of children. The possibility of such 

 a practical application has suggested to us some experiments with 

 especial reference to the safety and effectiveness of the injections. 



The proportion of toxin to antitoxiii in the mixture required to 

 produce immunization. — In May, 1 903, one of us reported some 

 experiments in which one set of horses were injected with mixtures 

 containing toxin .66 of L-f dose for each unit of antitoxin and 

 another with .66 of L-f for each 4 units of antitoxin. Three large 

 injections produced in the first series an average of 150 units, in 

 the second an average of 3 units in each c.c. of serum. 



Smith injected three guinea pigs with i unit plus i L+ dose, 

 2 units plus 1.3 L-|- dose, and 2 units plus i L-f dose respec- 

 tively. The litters born from the first and second animals showed 

 marked immunity at the end of eight months. The litter from the 

 third animal showed slight immunity at three months and none at 

 six months. 



These experiments indicate that while even a proportion of 6 

 units of antitoxin to i L4- of toxin produces slight immunity, the 

 toxin must be in proportion of more than i L-f dose to 2 units to 

 give marked and lasting effects. 



This brings us to the question of the safety of such mixtures. 

 The work of Morgenroth suggests that mixtures which are toxic 

 for one species are toxic for all. There is a difference, however, 

 among animals as to the amount of natural immunity and perhaps 

 therefore as to the development of serious symptoms or death from 

 a given quantity of toxin-antitoxin mixture. Even if all guinea 

 pigs lived, therefore, there would be a slight uncertainty in infants. 



