Multidisciplinary Approaches to Study O-Antigen: Antibody Recognition in Support of the Development of Synthetic Carbohydrate-Based Enteric Vaccines

Theillet, François‐Xavier; Chassagne, Pierre; Delepierre, Muriel; Phalipon, Armelle; Mulard, Laurence A.

doi:10.1007/978-3-7091-0870-3_1

Cited by 5 publications

(6 citation statements)

References 127 publications

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“…Analysis of Ab binding to the frame-shifted 10-mer segments [A 1 B 1 (E 1 )C 1 D 1 ] 2 and [D 1°A1 B 1 (E 1 )C 1 ] 2 also revealed divergence between the IgG fine specificity suggesting that chain length is not the sole important parameter. 92 In this respect, the unique behavior of IgG F22-4, which was also the only mAb showing measurable affinity to E 1 C 1 D 1 , was outlined.…”

Section: Molecular Insights On the Fine Specificity Of Murine Mab Binmentioning

confidence: 99%

“…89,91 It remains that single species O-Ag segments of defined length and composition are not easily available by detoxification and downsizing of the isolated biological material, suggesting the need for alternatives. In this respect, sustained progress in carbohydrate chemistry and conjugation chemistry, combined to advances in immunochemistry and structural biology, has permitted a better understanding of the fine specificity of bacterial polysaccharide recognition by monoclonal Abs (mAbs) 92 and deeper investigations in the field of synthetic carbohydrate-based conjugates. 93 Going beyond Ab binding, the ability of the latter conjugates to elicit Abs that recognize the natural surface polysaccharide antigens and protect against disease is a complex subject, also confronting interactions with cell surface receptors and antigen presentation.…”

Section: Synthetic Oligosaccharides As O-ag Surrogatesmentioning

confidence: 99%

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Classical and novel strategies to develop aShigellaglycoconjugate vaccine: from concept to efficacy in human

Barel

Mulard

2019

Human Vaccines & Immunotherapeutics

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Shigella are gram-negative bacteria that cause severe diarrhea and dysentery, with a high level of antimicrobial resistance. Disease-induced protection against reinfection in Shigella -endemic areas provides convincing evidence on the feasibility of a vaccine and on the importance of Shigella lipopolysaccharides as targets of the host humoral protective immune response against disease. This article provides an overview of the original and current strategies toward the development of a Shigella glycan-protein conjugate vaccine that would cover the most commonly detected strains. Going beyond pioneering “lattice”-type polysaccharide-protein conjugates, progress, and challenges are addressed with focus on promising alternatives, which have reached phases I and II clinical trial. Glycoengineered bioconjugates and “sun”-type conjugates featuring well-defined synthetic carbohydrate antigens are discussed with insights on the molecular parameters governing the rational design of a cost-effective glycoconjugate vaccine efficacious in preventing diseases caused by Shigella in the most at risk populations, young children living in endemic areas.

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Section: Molecular Insights On the Fine Specificity Of Murine Mab Binmentioning

confidence: 99%

Section: Synthetic Oligosaccharides As O-ag Surrogatesmentioning

confidence: 99%

Classical and novel strategies to develop aShigellaglycoconjugate vaccine: from concept to efficacy in human

Barel

Mulard

2019

Human Vaccines & Immunotherapeutics

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“…37 An experimental conjugate vaccine based on the pentadecasaccharide was shown to be protective in mice. 38 Further details are reviewed by Theillet et al 39 Similarly, for group A streptococci, although the branch point GlcNAc is immunodominant, two branched trisaccharide RU (-3Rhaa1-2[GlcNAcb1-3]Rhaa1-) 2 are required for effective recognition by sera 40 and the importance of an extended epitope has been confirmed by epitope mapping of a monoclonal antibody. 41 Cell-wall polysaccharide-reactive Abs are not elicited by immunization with epitopes smaller than a pentasaccharide.…”

Section: Glycoconjugate Vaccine Design Immunology and Immunochemistrymentioning

confidence: 99%

Designing a new antifungal glycoconjugate vaccine

Johnson

Bundle

2013

Chem. Soc. Rev.

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Bacterial capsular polysaccharides have been used as effective vaccines for adults but infants and seniors respond poorly to these immunogens because pure polysaccharides are unable to activate T-cells resulting in antibodies of low affinity and poor immunological memory. These deficiencies are addressed by conjugate vaccines composed of bacterial polysaccharide covalently attached to protein carriers such as tetanus or diphtheria toxoids. These vaccines activate T-cells and have been hugely effective in reducing the incidence of dangerous infectious diseases such as bacterial meningitis in infants and adults. The methods of conjugation often produce conjugate vaccines that contain polysaccharides with several cross links to one or more protein carrier molecules. Synthesis of large oligosaccharides derivatized to achieve single site attachment to protein has established the minimal size of an oligosaccharide that is required to produce protective antibody. Several examples are described where such oligosaccharides range in size from 8 to 16 monosaccharides. A more limited set of examples show that protective antibodies may be elicited by conjugate vaccines composed of tri and tetrasaccharide epitopes. One example is the β-mannan present in the phosphomannan glycoprotein of Candida albicans. Reverse engineering a protective antibody that recognizes this oligosaccharide revealed that a disaccharide was the minimal epitope. Further epitope mapping by functional group modification established that the internal mannose residue of a disaccharide was involved in the most important antibody-disaccharide interactions. NMR binding studies in combination with homology modeling of the bound β-mannan antigen suggested an optimum oligosaccharide for inclusion in a conjugate vaccine. Several conjugate vaccines were developed to test these conclusions. Immunization of mice or rabbits with conjugates containing disaccharide or trisaccharide conjugated to immunogenic proteins followed by live challenge experiments showed that the vaccines reduced fungal burden. The results of these and other studies suggest new approaches to novel synthetic conjugate vaccines.

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“…Those and the feasibility of larger fragments of the S. sonnei ZPSs add to the available arsenal of synthetic well‐defined zwitterionic oligosaccharides. They open the way to a detailed molecular investigation of the propensity of short oligosaccharides to act as antigenic, conformational, and structural mimic of the full length S. sonnei ZPSs [34a] . The gained knowledge will strengthen the exploration of the immunological properties of these puzzling ZPSs and the structure‐guided design of a S. sonnei synthetic glycan conjugate vaccine.…”

Section: Discussionmentioning

confidence: 96%

Exploratory N‐Protecting Group Manipulation for the Total Synthesis of Zwitterionic Shigella sonnei Oligosaccharides

Dhara

Mulard

2021

Chemistry A European J

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Shigella sonnei surface polysaccharides are well-established protective antigens against this major causeo fd iarrhoeal disease.T hey also qualify as unique zwitterionic polysaccharides (ZPSs)f eaturing ad isaccharide repeating unit made of two 1,2-trans linked rare aminodeoxy sugars, a 2-acetamido-2-deoxy-l-altruronic acid (l-AltpNAcA)a nd a2acetamido-4-amino-2,4,6-trideoxy-d-galactopyranose (AAT). Herein,t he stereoselective synthesis of S. sonnei oligosaccharides comprising two, three and four repeating units is reported for the first time. Severals ets of up to seven pro-tectingg roups wereexplored,s hedding light on the singular conformational behavior of protected altrosamine and altruronic residues. Ad isaccharide buildingb lock equipped with three distinct N-protectingg roups and featuring the uronate moiety already in place was designed to accomplish the iterative high yieldingg lycosylation at the axial 4-OH of the altruronate componenta nd achieve the challenging full deprotection step. Key to the successfulr oute was the use of a diacetyls trategy whereby the N-acetamido group of the l-AltpNAcAism asked in the form of an imide.

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Multidisciplinary Approaches to Study O-Antigen: Antibody Recognition in Support of the Development of Synthetic Carbohydrate-Based Enteric Vaccines

Cited by 5 publications

References 127 publications

Classical and novel strategies to develop aShigellaglycoconjugate vaccine: from concept to efficacy in human

Classical and novel strategies to develop aShigellaglycoconjugate vaccine: from concept to efficacy in human

Designing a new antifungal glycoconjugate vaccine

Exploratory N‐Protecting Group Manipulation for the Total Synthesis of Zwitterionic Shigella sonnei Oligosaccharides

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