Size fractionation of bacterial capsular polysaccharides for their use in conjugate vaccines

Costantino, Paolo; Norelli, Francesco; Giannozzi, Aldo; D'Ascenzi, Sandro; Bartoloni, Antonella; Kaur, Surinder; Tang, D; Seid, Robert C.; Viti, S; Paffetti, Roberto; Bigio, Massimo; Pennatini, Carlo; Averani, Giovanni; Guarnieri, Valentina; Gallo, Eugenia; Ravenscroft, Neil; Lazzeroni, Carla; Rappuoli, Rino; Ceccarini, Costante

doi:10.1016/s0264-410x(98)00348-x

Cited by 63 publications

(34 citation statements)

References 32 publications

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“…Present glycoconjugate vaccines against bacterial infections use either high-molecular-mass PSs or mixtures of large OSs obtained by structure-specific chemical degradations (2,7,16). The PSs have, to date, been randomly activated, and the final products are often difficult to characterize and control.…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity in a Mouse Model of a Conjugate Vaccine Made with a Synthetic Single Repeating Unit of Type 14 Pneumococcal Polysaccharide Coupled to CRM197

Mawas¹,

Niggemann

Jones

et al. 2002

Infect Immun

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Oligosaccharides (OSs) related to the pneumococcal type 14 capsular polysaccharide (Pn14PS) were studied for their ability to inhibit the binding between anti-PS14 antisera and native PS14. A synthetic tetrasaccharide corresponding to the repeating unit of the Pn14PS, a hexasaccharide mimic, and an octasaccharide fragment obtained by Pn14PS depolymerization were good inhibitors. CRM197 conjugates of the tetrasaccharide and an octasaccharide mimic were prepared by using either adipic acid diester or diethyl squarate linkers. The conjugate with the tetrasaccharide chains induced anti-Pn14PS antibodies when injected subcutaneously into mice, as determined by an enzyme-linked immunosorbent assay, and antibody titers increased with oligosaccharide loading. The adipic acid-linked tetrasaccharide conjugates elicited higher antibody titers than those prepared with a squarate spacer. The lower anti-Pn14PS antibody response of the octasaccharide mimic conjugate indicates the importance of the backbone galactose residue for an appropriate antibody response. The OS-CRM197 conjugate prepared from a single repeat unit of the Pn14PS is a potential vaccine candidate.Streptococcus pneumoniae is a major cause of morbidity and mortality in children and adults in both industrialized and developing countries (10). Although the licensed 14-and 23-valent pneumococcal capsular polysaccharide (PnPS) vaccines are safe and effective in reducing the incidence of invasive disease in healthy adults (5, 24), they are weakly immunogenic in children less than 2 years old and in the elderly, the two groups at highest risk (8,22,25,31). Whereas PSs are T-cellindependent immunogens, conjugates in which the PS is covalently attached to a protein carrier elicit a T-cell-dependent antisaccharide response even in infants, as evidenced by a booster effect upon subsequent immunizations. A number of PnPS serotypes have been conjugated to various carrier proteins and have been shown to be immunogenic and protective in various animal models (13,20,30) and in humans (1, 32). Intact PS, small oligosaccharides (OSs), or OSs of undefined length have been used to prepare those conjugates (3, 13, 36). The capsular polysaccharide of S. pneumoniae type 14 (Fig. 1) consists of a branched tetrasaccharide repeating unit (21) which is identical to the asialo core antigen of the type III group B Streptococcus PS (38). The poor immunogenicity of the Pn14PS compared to other PnPSs (18) may be due to structural similarities between antigenic determinants of the Pn14PS and human OS structures (e.g., human milk OSs and blood group carbohydrate structures). To avoid cross-reactivity with human tissue and the induction of autoreactive antibodies (6), we have been investigating the synthesis of well-defined OS fragments (26,27) corresponding to the Pn14PS to enable specific protective epitopes to be defined. Inhibition studies were performed both with synthetic OS structures and fragments from PS degradation to determine optimal OSs for conjugation. The protein carrier used in...

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Section: Discussionmentioning

confidence: 99%

Immunogenicity in a Mouse Model of a Conjugate Vaccine Made with a Synthetic Single Repeating Unit of Type 14 Pneumococcal Polysaccharide Coupled to CRM197

Mawas¹,

Niggemann

Jones

et al. 2002

Infect Immun

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“…These include quality and composition of the conjugates, conjugated methods, protein carriers, immunization routs, animal species, detecting methods, etc. (Costantino et al, 1999;Ada et al, 2003). Many studies have shown that in humans conjugated vaccines elicit antibodies to many pathogens, including N. meningitidis, Vibrio cholera, Haemophilus influenzae, Shigella sonnei, etc.…”

Section: Discussionmentioning

confidence: 99%

Measurement of opsonophagocytic activity of antibodies specific toNeisseria meningitidis serogroup A capsular polysaccharide-serogroup B outer membrane vesicle conjugate in animal model

et al. 2009

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Neisseria meningitidis is efficiently phagocytosed by polymorphonuclear leukocytes (PMN S ) following opsonization with opsonic antibodies; opsonophagocytosis is the primary mechanism for clearance of meningococci from the host. Thus, in testing meningococcal vaccines, the level of opsonophagocytic antibodies appears to correlate with vaccine-induced protection. Our previous studies demonstrated that the conjugation of N. meningitidis serogroup A capsular polysaccharide (CPSA) to serogroup B outer membrane vesicle (OMV) could induce a high level of bactericidal antibody response against serogroup A meningococci in animals. The purpose of this study was to evaluate opsonophagocytic activity of the conjugate of CPSA to OMV (CPSA-OMV). In order to evaluate the potential efficacy of CPSA-OMV a flow cytometric opsonophagocytic assay was used. The conjugate and controls were injected intramuscularly into four groups of rabbits with boosters on days 14, 28 and 42 following primary immunization. The rabbits were bled prior to injection and two weeks after each injection. Opsonophagocytic activity of antibodies in hyperimmune sera through rabbit PMN S were measured with flow cytometer, using dihydrorhodamine-123 as a probe. The results indicated that our conjugate could induce a highly significant level of opsonophagocytic activity against serogroup A meningococci after 56 days compared to the control groups (P<0.05). We conclude that this conjugate represents a vaccine candidate against serogroups A and B meningococci after further investigation.

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“…As described in Results, in some experiments, native MBPS derived from N. meningitidis group B strain MC58 was used for inhibition studies (referred to below as native MBPS to distinguish this polysaccharide from colominic acid). The native group B polysaccharide was isolated from culture supernatants as described by Costantino et al (6). All of the polysaccharide derivatives had an apparent mass of Ͼ10 kDa and an average apparent mass of 30 kDa, as determined by size exclusion chromotography calibrated with dextran and protein standards.…”

Section: Mabs the Anti-n-pr Mbps Murine Mab Seam 3 (Immunoglobulin G2bmentioning

confidence: 99%

Epitopes Recognized by a Nonautoreactive Murine Anti-N-Propionyl Meningococcal Group B Polysaccharide Monoclonal Antibody

Moe¹,

Dave²,

Granoff³

2005

Infect Immun

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Size fractionation of bacterial capsular polysaccharides for their use in conjugate vaccines

Cited by 63 publications

References 32 publications

Immunogenicity in a Mouse Model of a Conjugate Vaccine Made with a Synthetic Single Repeating Unit of Type 14 Pneumococcal Polysaccharide Coupled to CRM197

Immunogenicity in a Mouse Model of a Conjugate Vaccine Made with a Synthetic Single Repeating Unit of Type 14 Pneumococcal Polysaccharide Coupled to CRM197

Measurement of opsonophagocytic activity of antibodies specific toNeisseria meningitidis serogroup A capsular polysaccharide-serogroup B outer membrane vesicle conjugate in animal model

Epitopes Recognized by a Nonautoreactive Murine Anti-N-Propionyl Meningococcal Group B Polysaccharide Monoclonal Antibody

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