"Natural" antibodies to representative species of Enterobacteriaceae were found to be principally associated with the γ1-macroglobulin prepared from Cohn fraction III-I of pooled human plasma. The amount of antibodies present was estimated by measuring the bactericidal, hemagglutinating, mouse-protective, and opsonophagocytic activities of this fraction. Comparison with the antibody activity of γ2-globulin of Cohn fraction II showed that up to 100 times more antibody activity on a weight basis was present in the macroglobulin fraction. These findings suggest that differences between natural and immune antibody result from the physicochemical properties of 2 different classes of immune globulin.

A partially purified M protein, extracted from a mouse-virulent strain of type 3, group A streptococcus, was administered subcutaneously in gradually increasing amounts at weekly intervals to 21 children in a Family Program. Seven children with type 3 bactericidal antibody in prevaccination sera showed a secondary response. Of 14 children with no detectable type 3 bactericidal antibody prior to vaccination, 13 developed definite type 3 antibody during or soon after vaccination. This response appeared to be of the primary variety in at least some of the 13 children because (i) the total incidence of antibody response (20 of 21) was greater than can be accounted for by the documented incidence of clinical and subclinical type 3 infections among children of our Family Program during a period of 14 years, (ii) the response in the 13 children with no detectable antibody prior to vaccination was more delayed than in those showing a definite secondary response, and (iii) on the average, the amount of vaccine needed for a response in these 13 children was 15 to 28 times greater than that required for the secondary response. Local skin reactions were variable among the vaccinated children. Systemic reactions were infrequent and not severe. The giving of multiple injections of partially purified M protein did not seem to cause cutaneous hypersensitivity.

AIICHAEL, J. GABRIEL (House of the Good Samaritan, Children's Hospital M\edical Center, 13oston, Mass.), BENEDICT F. MIASSELL, AND ROBERT E. PERKINS. Effect of sublethal concentrations of penicillin on the virulence and antigenic composition of group A streptococci. J.Bacteriol. 85:1280-1287. 1963.---Virulent strains of group A streptococci were grown in sublethal concentrations of penicillin and tested for possible changes in colonial morphology, virulence, and antigenic composition. After overnight growth in broth containing penicillin, there was a marked reduction in precipitable group A and M protein content of the bacteria. Upon transfer to broth without antibiotic, the streptococci regained their ability to produce these substances. After multiple transfers in broth containing nonbactericidal levels of penicillini, variants developed which lacked group and type substances and which were also relatively resistant to penicillin. These variants were avirulent for mice and