Reactions of Human Subjects to the Injection of Purified Type Specific Pneumococcus Polysaccharides 1

Abstract

By subjecting pneumococcus filtrates to ultrafiltration followed by repeated fractional precipitation with alcohol, Wadsworth and Brown (1) have obtained good yields of type-specific and species-specific polysaccharides in a relatively high state of purification. This report deals with the local reactions and the type-specific antibody response of non-pneumonic human subjects to injections of specific polysaccharides of Types I, IV, V, VII, and XIV pneumococci prepared by this method. (4,5) and also by Alston, Galbraith, and Stewart (6). Similar skin reactions were also elicited with varying frequency, using polysaccharides prepared by the same and by other methods, in normal subjects and in hospital subjects without pneumonia or recent intracutaneous injections (7,8,9,10). In such subjects, positive reactions to the initial injections were not correlated with the presence of circulating antibodies (7, 8, 9, 10) but the development of antibodies for the homologous pneumococcus type was stimulated by a single or by multiple intracutaneous injections (8,9,11,12).Alston and Lowden (10), using Type I and Type II specific polysaccharides prepared by the methods of Heidelberger, Sia, and Kendall (13) and of Heidelberger and Avery (14), respectively, observed in normal sub-1 This study was aided, in part, by a grant given in honor of Francis Weld Peabody by the Ella Sachs Plotz Foundation. jects a secondary cutaneous reaction consisting of redness, edema, and tenderness occurring in 2 to 5 hours and lasting 8 to 48 hours. A similar reaction had also been described by Finland and Sutliff (4) in occasional patients recovering from pneumonia in whom the reactions, induced by similar polysaccharides, were typespecific and began as a typical but intense immediate wheal and erythema. Similar reactions, both with and without the characteristic immediate phase were also noted in non-pneumonic subjects tested with autolysates from virulent and from avirulent strains (7).Tillett and Francis (15) and later Ash (16) demonstrated precipitins for the somatic, species-specific, carbohydrate, the so-called C fraction of Tillett, Goebel, and Avery (17), in the febrile stage of pneumonia and of many other acute infections but not after recovery from these diseases. Francis and Abernethy (18) reported immediate and delayed reactions, similar to those described above, which they obtained with the C fraction during the height of pneumonia and other febrile illnesses but not during convalescence and not in cases having a fatal termination.Differences in antigenic activity of type-specific carbohydrate substances derived in different ways from the same type of pneumococcus have been observed by many workers (19 to 27 inc.). Wadsworth and Brown (19) found that all of their so-called cellular carbohydrates contain phosphorus and nitrogen, produce purpura in mice, and differ from the corresponding soluble specific substance prepared by the earlier methods of Heidelberger, Avery, and others in their reaction with immune serums and in the respon...

Polyfunctional Dinitrophenyl Haptens as Reagents for Elicitation of Immediate Type Allergic Skin Responses

“…DNP-polylysines bear a number of interesting resemblances to purified pneumococcal polysaccharides. Both of these polymers combine effectively with antibody in vivo and in vitro and elicit a variety of immediate allergic responses (18,21). The purified pneumococcal polysaccharides can, however, stimulate a significant antibody response (19).…”

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

“…The demonstration by Francis and Tillett (1) and others (2)(3)(4)(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.…”

Adventures with antibacterial drugs

“…53 • 54 • 65 We first investigated various pneumococcus products, some of which we prepared and tested, mostly by the intracutaneous route, 5 5 and studied the antibody response of different dosages and routes of inoculation of some purified type-specific products. 28 Felton, which produced heterologous as well as homologous type-specific antibodies in laboratory animals, were also tested in human subjects with similar results and were reported by Felton, Sutliff, and Steele. 18 In the first of these studies, single intra- cutaneous injections of 0.01 mg. of proteinfree type-specific polysaccharides of either Type I, II, or III, or four similar daily injections, were followed in most of the human subjects tested by the appearance of antibodies against the homologous but not against heterologous types of pneumococci.…”