ANTIGENICITY OF PNEUMOCOCCUS 331 



cure the most effective secondary stimulus, gave injections at in- 

 tervals of fourteen instead of four or eight days. 



The question of the effect of heat on the immunizing activity of 

 Pneumococcus was subjected to systematic study by Barnes and 

 White, 86 who compared the antibody response following the injec- 

 tion into rabbits of heat-killed and formalinized cultures of Type I 

 Pneumococcus, administered according to different schedules over 

 long periods — in some of the experiments for as long as eight 

 months. As antigens, the authors used saline suspensions of the 

 sediment from eighteen-hour broth cultures of a virulent Type I 

 strain, subjected to 56° in a water-bath for one hour, and similar 

 suspensions of culture sediment treated with 0.3 per cent formalin. 

 The vaccines were standardized by the Gates 504 nephelometer and 

 the individual doses accurately measured. The injections were given 

 intravenously according to three different plans somewhat similar 

 to those of Yoshioka and of Killian. The schedules consisted re- 

 spectively of a single injection on each of three successive days; a 

 single injection on each of five successive days ; and a series of six 

 injections on each of the first two days with the other four on the 

 third day. The rest periods varied from one to three weeks, and 

 test bleedings were usually taken seven, twelve, and, in some in- 

 stances, twenty-two days after the last injection of a series. The 

 various serum samples were titrated for agglutinins, precipitins, 

 and mouse-protective antibodies. 



Heat-killed pneumococci produced highly potent serums of strict 

 type-specificity. The first and third named methods were equally 

 productive, but the first was the method of choice because of its 

 greater simplicity. The results of the study, besides confirming the 

 value of heat-killed pneumococci in establishing a high degree of 

 immunity, afforded a rational basis for the immunizing treatment 

 of horses for the production of therapeutic serum. 



OTHER DEVITALIZED ANTIGENS 



As soon as it was found that heat-killed pneumococci were capa- 



