Comparative immunogenicities of Vi polysaccharide-protein conjugates composed of cholera toxin or its B subunit as a carrier bound to high- or lower-molecular-weight Vi

Szu, Shousun C.; Li, Xiuru; Schneerson, Rachel; Vickers, James H.; Bryla, Dolores A.; Robbins, John B.

doi:10.1128/iai.57.12.3823-3827.1989

Cited by 96 publications

(57 citation statements)

References 36 publications

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“…The immune moiety elicited by Vi, like that elicited by other capsular polysaccharidebased vaccines, is mainly serum antibody (55)(56)(57). The surface polysaccharide of S. paratyphi A alone is not immunogenic in mice, most likely because of its comparatively low M r (51,66). There is experimental evidence that serum antibodies to the O-specific polysaccharides of group B and D salmonellae, whether actively induced or passively administered, confer protection to mice (12,16,55,56,63,72).…”

Section: Discussionmentioning

confidence: 99%

Synthesis, characterization, and immunological properties in mice of conjugates composed of detoxified lipopolysaccharide of Salmonella paratyphi A bound to tetanus toxoid with emphasis on the role of O acetyls

et al. 1996

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Salmonella paratyphiA, the second most common cause of enteric fever in Southeast Asia, is a habitant of and a pathogen for humans only. Lipopolysaccharides (LPS) are both essential virulence factors and protective antigens for systemic infections caused by groups A, B, C, and D nontyphoidal salmonellae. The O-specific polysaccharide of S. paratyphi A is composed of a trisaccharide, 32-␣-D-Manp-(134)-␣-L-Rhap-(133)-␣-D-Galp-(13, with a branch of D-paratose from the C-3 of ␣-D-mannose, and the C-3 of ␤-L-rhamnose is partially O acetylated (C. G. Hellerqvist, B. Lindberg, K. Samuelsson, and A. A. Lindberg, Acta Chem. Scand. 25:955-961, 1971). On the basis of data from our investigational vaccines for enteric bacterial pathogens, including group B salmonellae (D. C. Watson, J. B. Robbins, and S. C. Szu, Infect. Immun. 60:4679-4686, 1992), conjugates composed of the detoxified LPS of S. paratyphi A bound to tetanus toxoid (TT) were prepared by several schemes. LPS was detoxified with acetic acid or with hydrazine; the latter removed O acetyls from the O-specific polysaccharide. The detoxified polysaccharides were activated with cyanogen bromide (CNBr) or with 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) and bound to TT with or without a spacer. Solutions of 2.5 g of saccharide, alone or as a conjugate, were injected subcutaneously into young mice, and LPS and TT antibodies were measured by enzyme-linked immunosorbent assaying. A conjugate synthesized with highermolecular-weight O-SP elicited the highest anti-LPS levels. Only conjugates with O acetyls elicited serum immunoglobulin G anti-LPS with bactericidal activity. There were no statistically significant differences between LPS antibody levels elicited by conjugates synthesized with or without a spacer. The conjugate with O-specific polysaccharide activated by CDAP and bound to TT without a spacer elicited the highest level of TT antibodies. Clinical evaluation of S. paratyphi A conjugates is planned.Reagents. Anhydrous hydrazine, adipic acid dihydrazide (ADH), 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP), 1-ethyl-3(3-dimethylaminopropyl) carbodiimide (EDAC), RNase, and DNase I were from Sigma Chemical Co., St. Louis, Mo.; 2,4,6-trinitrobenzenesulfonic acid (TNBS) and bicinchoninic acid were from Pierce Chemical Co., Rockford, Ill.; cyanogen bromide (CNBr) was from Eastman Kodak Co., New Haven, Conn.; proteinase K was from Boehringer Mannheim Biochemicals, Indianapolis, Ind.; acetic acid was from Mallinckrodt Specialty Chemicals Co., Paris, Ky.; Sephadex G-75, Sepharose CL-6B, Superose 12, and dextrans for calibration of molecular sizes were from Pharmacia LKB Biotechnology, Inc., Piscataway, N.J.; affinity-purified, alkalinephosphatase-labeled goat antibodies to mouse Ig were from Kirkegaard and Perry Laboratories, Inc., Gaithersburg, Md.; Limulus polyphemus amoebocyte lysate (LAL) was from Associates of Cape Cod, Woods Hole, Mass.; disodium 4-nitrophenyl phosphate hexahydrate was from Fluka, Ronkonkoma, N.Y.; pyrogen-free saline (PFS)...

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Section: Discussionmentioning

confidence: 99%

Synthesis, characterization, and immunological properties in mice of conjugates composed of detoxified lipopolysaccharide of Salmonella paratyphi A bound to tetanus toxoid with emphasis on the role of O acetyls

et al. 1996

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“…One reason for this is probably that CTB binds to GM1 ganglioside receptors including those on M cells and thereby facilitates uptake of the antigen (21,22). CTB and CT have been used successfully as carriers for PS antigens, Vi from Salmonella typhi (45), and V. cholerae LPS (18), but these conjugates were not intended for mucosal administration. We used CT as a mucosal adjuvant since it is one of the best-characterized mucosal adjuvants so far, with a proven effect (21,22).…”

Section: Discussionmentioning

confidence: 99%

Local and systemic antibody responses to dextran-cholera toxin B subunit conjugates

et al. 1995

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This study was designed to test local and systemic immunity following mucosal immunization with a polysaccharide-protein conjugate. After preparing and characterizing dextran-cholera toxin B subunit (CTB) conjugates, we studied their immunogenicity in mice following systemic or mucosal immunizations. Dextran was chosen as a model polysaccharide antigen and conjugated via adipic acid dihydrazide and N-succinimidyl-3-(2-pyridyldithio)propionate to CTB. Mice were immunized either subcutaneously, intranasally, or perorally three times, and cholera toxin was used as an adjuvant for the mucosal immunizations. Three conjugates with different molecular weights for dextran (40,000 and 76,000) or varying dextran/CTB molar ratios were tested. Peroral immunizations with all conjugates evoked local immunoglobulin A (IgA) antibody responses against dextran in the small intestine, and intranasal immunizations did the same in the lung. Intranasal immunizations also elicited serum antibody titers that were significantly higher than or equal to those after subcutaneous immunizations. Intranasal immunizations evoked serum IgG antidextran titers which were dependent on the dextran/CTB molar ratio and inversely related to the local IgA response, which was not the case for subcutaneous immunizations. This is the first study of local and systemic immunity following mucosal immunization with a polysaccharide-protein conjugate. The results show that it is possible to evoke a local as well as a systemic antibody response against a polysaccharide by conjugating it to CTB and using an appropriate route of immunization.

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“…In an attempt to increase the immunogenicity of Vi as a parenteral vaccine, Szu et al (37) conjugated Vi polysaccharide to tetanus toxoid, diphtheria toxoid and cholera toxin, conferring T-dependent properties on the polysaccharide. The candidate conjugate vaccine elicited higher levels of serum antibodies than purified Vi alone in two animal species, mice and rhesus monkeys (38).…”

Section: Discussionmentioning

confidence: 95%

“…The molecular weight of polysaccharides is an important factor for their immunogenicity. Earlier, it was observed that Vi ( -45 kD) prepared by ultrasonic irradiation, which does not alter the structure of its monomeric units, is less immunogenic as a conjugate than is native Vi in mice (36,38). Therefore, we conjugated porin to native Vi.…”

Section: Discussionmentioning

confidence: 99%

Protective Efficacy and Immunogenicity of Vi‐Porin Conjugate against Salmonella typhi

Singh

Ganguly

Kumar

et al. 1999

Microbiology and Immunology

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A conjugate vaccine against Salmonella typhi was prepared by covalently binding capsular polysaccharide (Vi) with porin, both isolated from S. typhi. First, Vi and porins were extracted. The Vi was purified from S. typhi Ty2. The purified Vi conformed to the requirements of the World Health Organization. Porins were purified from S. typhi 0901. The Vi was bound to the porins by a heterobifunctional cross‐linking reagent, N‐succinimidyl‐3‐(2‐pyridyl dithio)‐propionate (SPDP). After preparing the Vi‐porin conjugate, its protective ability and immunogenicity were studied in mice following systemic immunization. The results showed that the conjugate is 6.5‐fold more protective than Vi alone against S. typhi. The mice immunized with conjugate elicited higher anti‐Vi antibody (IgG) levels (P<0.01) than the mice immunized with Vi alone. Anti‐porin antibodies were also induced by the conjugate. To study the mucosal immune responses, secretory IgA (sIgA) in the intestinal fluid was measured. Conjugate‐immunized mice showed the induction of sIgA as compared to Vi alone. The results showed that when Vi is bound to porins, both isolated from same organism, the resultant conjugate induced both systemic and mucosal immune responses and provided better protection against S. typhi than Vi alone.

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Comparative immunogenicities of Vi polysaccharide-protein conjugates composed of cholera toxin or its B subunit as a carrier bound to high- or lower-molecular-weight Vi

Cited by 96 publications

References 36 publications

Synthesis, characterization, and immunological properties in mice of conjugates composed of detoxified lipopolysaccharide of Salmonella paratyphi A bound to tetanus toxoid with emphasis on the role of O acetyls

Synthesis, characterization, and immunological properties in mice of conjugates composed of detoxified lipopolysaccharide of Salmonella paratyphi A bound to tetanus toxoid with emphasis on the role of O acetyls

Local and systemic antibody responses to dextran-cholera toxin B subunit conjugates

Protective Efficacy and Immunogenicity of Vi‐Porin Conjugate against Salmonella typhi

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