Preparation of the Type-Specific Polysaccharide of the Type I Meningococcus and a Study of Its Effectiveness as an Antigen in Human Beings

Abstract

The demonstration by Francis and Tillett (1) and others (2-5) that the typespecific polysaccharides of pneumococci are antigenic in man and induce the production of antibodies in humans which protect mice against subsequent injection of virulent organisms, has led to numerous attempts to use these purified polysaccharides in active immunization (4, 6). Since the antipolysaccharide in Type I antimeningococcal sera has also been found to be effective in protecting mice, the capacity of several preparations of Type I meningococcal polysaccharide to induce precipitin formation in human volunteers was studied. Use was made of the colorimetric micro method for the estimation of antibody developed by Heidelberger and MacPherson (7) and applied in a study of the antibody response accompanying convalescence from pneumonia (8).Preparations of the specific polysaccharide of the Type I meningococcus have been made and characterized by Scherp and Rake (9). Their materials, however, were shown to contain at least 20 per cent of a second substance which reacted with antimeningococcal sera (10) but was found not to remove protective antibody (11). A sample of polysaccharide (preparation 18 (9)) was generously supplied by Dr. H. W. Scherp for use in this investigation. In addition, since both glacial acetic acid and barium hydroxide had been used in purifying their polysaccharide, several lots were prepared in which the use of these fairly drastic reagents was avoided. The chemical and immunological properties of these materials were studied and it was found that, unlike preparation 18, they showed only a slight zone in the quantitative precipitin reaction where both antigen and antibody could be detected in the supernatant. No evidence 6f precipitin formation in humans was obtained with preparation 18, but in a few instances a small but significant antibody response to injection of *

Human Immunity to the Meningococcus

“…Both the A and the C polysaccharides proved to be good immunogens in man. This result is at variance with previous experiments (7,8), but the polysaccharides tested prior to the present study were probably less than 50,000 average molecular weight (9). 1 It is our belief that the high molecular weight of the polysaccharides used in this study accounts for their immunogenicity, a hypothesis, which, however, has not been tested directly.…”

“…Kabat et al (7) investigated the immunogenicity of the group A polysac. charide in human volunteers.…”

Vaccines for prevention of meningococcal disease

“…In early attempts in the 1940s to prepare purified group A meningococcal PS vaccines, the PS was found to be almost nonimmunogenic (20). Later studies by Gotschlich et al (15) showed that the early failures were due to degradation of the PS.…”

The meningococcus and mechanisms of pathogenicity.

“…Roberts (250) reported that the anticapsular antibodies in serum against group A and C polysaccharides are responsible for most of the opsonic activity against meningococci. Kabat et al (169) in 1945 attempted to induce in human subjects antibody to meningococcal capsular polysaccharides, but failed, probably because of the small molecular weight of their preparations (<50,000 daltons), which failed to stimulate antibody. Gotschlich et al (124) developed an extraction and purification method that yielded polysaccharides from groups A, B, and C with molecular weights of >100,000.…”