Serum antibody response in adult volunteers elicited by injection of Streptococcus pneumoniae type 12F polysaccharide alone or conjugated to diphtheria toxoid

Abstract

Conjugates of an uronic acid-containing capsular polysaccharide (CP), pneumococcous type 12F (Pn12F) bound to diphtheria toxoid (DT), were studied for safety and immunogenicity in adult volunteers. In mice, these conjugates, prepared with the same lot of DT and Pnl2F-40234-006, a homogenous CP of high molecular weight, or Pnl2-812408, a polydisperse CP with lower-molecular-weight material, were more immunogenic than the Pnl2F alone and had T-cell dependent properties (Infect. Immun. 56:2292Immun. 56: -2298Immun. 56: , 1988. Adult volunteers, randomized into three groups, were injected either with one of these two conjugates or with Pnu-Imune, the 23 valent pneumococcus vaccine containing 25 ,ug of Pn12F as one of its components.Volunteers were injected two times, 4 weeks apart, with the Pnl2F-DT conjugates and once with the Pnu-Imune. Side reactions following injection of the conjugates or Pnu-Imune were mild and short-lived. At 4 weeks and at 7 months after the first injection, higher levels of Pnl2F antibodies were found in the volunteers injected with the conjugates than in the Pnu-Imune group (P < 0.001). The conjugate prepared with the higher-molecular-weight Pnl2F elicited higher levels of antibodies than the conjugate prepared with a lower-molecular-weight Pn12F preparation (P = 0.05). Both conjugates elicited about a 13-fold rise in DT antibodies.

Synthesis and immunologic properties in mice of vaccines composed of Staphylococcus aureus type 5 and type 8 capsular polysaccharides conjugated to Pseudomonas aeruginosa exotoxin A

“…The molecular sizes of S. aureus type 5 and type 8 CPs, assayed by the method used for vaccines, are lower than those of the CPs of meningococci, pneumococci, and H. influenzae type b (15). As with observations with the H. influenzae type b CP, the S. aureus type 5 and 8 CPs alone thetic scheme, have both increased immunogenicity and acquired T-cell-dependent properties, including higher IgG antibody levels, in adult volunteers (13). Similar improvements in the immunologic properties in mice and in monkeys are conferred to Vi-protein conjugates by this method (51).…”

“…The amount of CP synthesized by bacteremic isolates is comparatively low; incubation of these strains with India ink does not demonstrate the CP as it does the large capsule surrounding the Smith strain (type 2 according to the classification of Kar- poor immunogens in humans, especially in patients with reduced resistance (15,47). Conjugating these CPs to proteins, as has been done for other polysaccharides, would be expected to enhance their immunogenicity both for active immunization and for preparing high-titered antisera in volunteers for passive immunization (13,14,46,47,51).…”

Synthesis, characterization, and some immunological properties of conjugates composed of the detoxified lipopolysaccharide of Vibrio cholerae O1 serotype Inaba bound to cholera toxin

“…On the basis of these observations, we developed detoxified LPS-protein conjugate vaccines in order to elicit a vibriocidal antibody response with T-cell-dependent properties (49). The preparation of conjugates to elicit LPS antibodies is difficult because (i) the complete structures of the LPS of the two serotypes are not known and (ii) the size of the Inaba O-SP is relatively small (-6,000 Da) (the immunogenicity of saccharides alone or in conjugates is directly related to their size) (2,17,53). Acidic hydrolysis of LPS from strain 569B (Inaba) resulted in a product of -5,900 Da that had clinically acceptable levels of endotoxin but which did not precipitate with hyperimmune sera.…”

Synthesis of a conjugate vaccine composed of pneumococcus type 14 capsular polysaccharide bound to pertussis toxin

“…Analyses. Polysaccharide was measured by the anthrone reaction with Pnl4 as a standard (10). Adipic acid hydrazide was measured by the 2,4,6-trinitrobenzenesulfonic acid reaction with adipic acid dihydrazide as a standard (9).…”

“…The development of polysaccharide protein conjugates for prevention of systemic infections caused by Haemophilus influenzae type b serves as a precedent for making conjugates of polysaccharides of other capsulated pathogens (31). This technology has been extended to improve the immunologic properties of other polysaccharides of medically important organisms such as Streptococcus pneumoniae (5,9,10,25,26,31,38,39). Since the objective is to provide protection against many capsulated bacterial pathogens of infants and children, investigators have used established vaccines such as diphtheria and tetanus toxoids or potentially protective antigens such as the toxoids of Pseudomonas aeruginosa exotoxin A and pneumococcal hemolysin (3,7,23,24).…”