PRODUCTION OF ANTIPNEUMOCOCCIC SERUM 535 



apparatus to a corrected reading of 2.0 centimeters in a 1 to 30 

 dilution of the standard suspension — approximately twenty-five 

 billion organisms per cubic centimeter. Formerly, the doses were 

 given in gradually increasing amounts until "holding doses" of 

 9.0, 10.0, and 10.0 cubic centimeters, or a maximum of about 250 

 billion pneumococci, were administered. More recently, the doses 

 have been decreased, so that the usual amounts are approximately 

 one-fourth (2.0, 2.5, 2.5 cubic centimeters of the standard suspen- 

 sion) of those previously used. The content of protective sub- 

 stances of the serum produced under the present scheme is as great 

 as, if not greater than, it was when larger amounts of vaccine were 

 used. It must be noted, however, that because horses vary widely 

 in their response to injections of bacterial suspensions it is occa- 

 sionally necessary in individual instances to decrease the dose still 

 further. 



Spacing. The spacing of injections of vaccines is important. In 

 earlier investigations, the antigens were usually administered at 

 weekly intervals. Wadsworth and Kirkbride 1470 began the immuni- 

 zation process by giving injections either weekly or on three suc- 

 cessive days. Cole 257 scheduled injections daily for seven days as a 

 single series, with a rest interval of a week, followed by seven more 

 daily injections. Cole and Moore 268 gave injections of dead organ- 

 isms daily for six or seven days, with a rest of a week, then a series 

 of three daily doses of live organisms with an interval of a week 

 between each series. Avery, Chickering, Cole, and Dochez 36 recom- 

 mended the following procedure: Six daily injections of heat-killed 

 vaccines were given, followed by an interval of seven days, after 

 which a second series of six daily doses was administered. Injec- 

 tions of living organisms were then made on three successive days, 

 followed by a rest of seven days, when three consecutive daily doses 

 were again given. This routine was followed throughout the course 

 of immunization. 



Using dried antigen, Truche 1420 gave injections on ten succes- 

 sive days and, after the lapse of from ten days to a fortnight, in- 



