Vaccination of Rabbits Against Pneumococci with Special Reference to Oral Immunization. ∗

Abstract

The use of pneumococcus vaccines by oral administration is largely based upon the investigations of Ross 1 and in an article on prophylactic immunization of rabbits against pneumococcus pneumonia and septicemia Kolmer and Rule 2 found that 7 daily doses of vaccines by oral administration engendered a high degree of immunity against Type I pneumococcus, somewhat less against Type II and still less against Type III, as determined by the intratracheal injection of virulent cultures of these types. Kolmer and Amano 3 also observed that rabbits may be effectually immunized against meningitis and septicemia following intratympanal and in-tracisternal injections of virulent Types I, II and III pneumococci, by the oral administration of vaccines given once a day for a week. Particularly encouraging results were observed with HCl acid-killed, sodium taurocholate-dissolved and heat-killed milk cultures of virulent pneumococci and it was recommended that when time permits, humans with pneumococcus paranasal sinusitis and otitis be prepared for operative procedures by the oral immunization of autogenous vaccines as a possible protection against extension of the infection to the meninges.

These investigations were continued with rabbits to determine: (1) dosage of vaccine by oral administration in relation to acquired immunity; (2) duration of immunity after oral immunization; (3) to compare the immunity response from subcutaneous injections with oral administration of the vaccines.

Since “acid-killed” pneumococcus vaccines appeared to engender the highest degree of immunity in rabbits 2 they were mostly employed. The organisms were cultivated in a broth medium for 24 hours and sufficient N/1 hydrochloric acid added to give an N/15 concentration. After standing for 2 hours at room temperatures the vaccines were subcultured for sterility. Numerically they averaged about 500 million per cc. The dosage was 0.2, 0.5, 1.0, 2.0, and 5.0 cc. per kilo administered daily for 7 doses by stomach tube. Numerically the dosage varied therefore from approximately 100 to 2500 million per kilo of weight. One week after the last dose each animal, including normal controls, was given intratracheal injections of living broth cultures. Immediately or within a few hours after death the heart blood was cultured for pneumococci and complete necropsies performed with special reference to the lungs.

Summary. 1. Vaccination of rabbits against Types I, II and III pneumococcus by oral administration of acid-killed vaccines requires rather large doses amounting approximately to 1000 million per kilo of weight, although smaller doses (100 million per kilo) were sometimes effective, especially in the case of Type I pneumococcus. 2. One dose of 1000 million Type I acid-killed vaccine by oral administration sometimes produced effective immunization but best results were observed with a minimum of 5 doses at daily intervals. 3. Pneumococcus immunity after oral administration of Type I acid-killed vaccine is of short duration as determined by survival after intratracheal injections of virulent culture. One month after vaccination the degree of immunity is decreased, and practically extinct at the end of 6 months. 4. The subcutaneous injection of rabbits with a chemically killed vaccine containing a total of 60 million of Types I, II and III per cc. gave a better immunity response than an acid-killed vaccine of the same strength by oral administration in dose of 1 cc. per kilo of weight.