Observations on the immunization of rabbits with single strain and combined multiple strain vaccines

Previous to 1916, the Army and the National Guard were immunized with typhoid vaccine. During the late summer and early autumn of that year, numerous cases of paratyphoid fever developed among the troops along the Mexican border, and the Army medical authorities therefore felt it desirable to substitute a triple vaccine, of typhoid bacilli combined with the paratyphoids A and B, for the single strain typhoid vaccine then being issued. Similar experience with paratyphoid in the British Army in Flanders in the same year had also resulted there in the adoption of a combined vaccine.

This immediately brought up the question as to the basis for the use of combined vaccines for prophylactic inoculation and led to the initiation, in the winter of 1917, of the experiments here presented. Other workers in this field had preceded us. Castellani 1 in 1903, showed that on injecting an animal with two different organisms at the same time, agglutinins were produced for both, and that the amount of agglutinin for each of the two organisms was about the same as in those animals inoculated with but one type of organism only. Subsequently he stated that as many as six different types of bacteria might be combined in a single vaccine with this same result, but that if more than six types were combined, a diminished amount of agglutinin for each type resulted. The problem has been attacked by other investigators, who have followed the methods of Castellani, by comparing the agglutinin formation when single and combined vaccines were employed. As we have long known that agglutinin formation is not a real index of the degree of immunity, it has seemed desirable that further study of the problem should be made, in observing the relative amounts of bacteriolysins produced.