Engineering a new generation of carbohydrate-based vaccines

Weyant, Kevin B.; Mills, Dominic C.; DeLisa, Matthew P.

doi:10.1016/j.coche.2017.12.009

Cited by 15 publications

(5 citation statements)

References 73 publications

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“…We will discuss examples involving chemical modifications of the carbohydrates, especially the covalent conjugates of antigens and carbohydrate-based delivery carrier or adjuvants. Vaccines that contain carbohydrates and derivatives only as antigen components, or natural carbohydrates encapsulated/admixed with other vaccine components, have been reviewed (Marzabadi and Franck, 2017;Colombo et al, 2018;Wei et al, 2018;Weyant et al, 2018;Jin et al, 2019;Micoli et al, 2019), and are not discussed here.…”

Section: Introductionmentioning

confidence: 99%

Carbohydrate Conjugates in Vaccine Developments

Lang

Huang

2020

Front. Chem.

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Vaccines are powerful tools that can activate the immune system for protection against various diseases. As carbohydrates can play important roles in immune recognition, they have been widely applied in vaccine development. Carbohydrate antigens have been investigated in vaccines against various pathogenic microbes and cancer. Polysaccharides such as dextran and β-glucan can serve as smart vaccine carriers for efficient antigen delivery to immune cells. Some glycolipids, such as galactosylceramide and monophosphoryl lipid A, are strong immune stimulators, which have been studied as vaccine adjuvants. In this review, we focus on the current advances in applying carbohydrates as vaccine delivery carriers and adjuvants. We will discuss the examples that involve chemical modifications of the carbohydrates for effective antigen delivery, as well as covalent antigen-carbohydrate conjugates for enhanced immune responses.

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Section: Introductionmentioning

confidence: 99%

Carbohydrate Conjugates in Vaccine Developments

Lang

Huang

2020

Front. Chem.

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“…Only CPS3 and CPS37 are synthesized through the synthase-dependent pathway. S. pneumoniae CPS 4, 8, 5, and 12F were successfully assembled in the gram-negative bacterium E. coli , which facilitated the development of bioconjugate vaccines using protein glycan-coupling technology ( 4 , 56 ). Here, we further confirmed that S. pneumoniae CPS2, 3, 5, 6A, 9V, 14, and 18C could be successfully synthesized in the RASV system, which broadens the application of gram-negative bacteria for the synthesis of gram-positive CPSs.…”

Section: Discussionmentioning

confidence: 99%

Synthesis and delivery ofStreptococcus pneumoniaecapsular polysaccharides by recombinant attenuatedSalmonellavaccines

Liu

Bian

et al. 2020

Proc. Natl. Acad. Sci. U.S.A.

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Streptococcus pneumoniae capsular polysaccharides (CPSs) are major determinants of bacterial pathogenicity. CPSs of different serotypes form the main components of the pneumococcal vaccines Pneumovax, Prevnar7, and Prevnar13, which substantially reduced the S. pneumoniae disease burden in developed countries. However, the laborious production processes of traditional polysaccharide-based vaccines have raised the cost of the vaccines and limited their impact in developing countries. The aim of this study is to develop a kind of low-cost live vaccine based on using the recombinant attenuated Salmonella vaccine (RASV) system to protect against pneumococcal infections. We cloned genes for seven different serotypes of CPSs to be expressed by the RASV strain. Oral immunization of mice with the RASV-CPS strains elicited robust Th1 biased adaptive immune responses. All the CPS-specific antisera mediated opsonophagocytic killing of the corresponding serotype of S. pneumoniae in vitro. The RASV-CPS2 and RASV-CPS3 strains provided efficient protection of mice against challenge infections with either S. pneumoniae strain D39 or WU2. Synthesis and delivery of S. pneumoniae CPSs using the RASV strains provide an innovative strategy for low-cost pneumococcal vaccine development, production, and use.

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“…However, since most pure carbohydrate antigens are T-cell independent, such vaccines usually have weak immunogenicity by directly interacting with B cells, producing low titers of low-affinity IgM antibodies. To overcome this problem, carbohydrate antigens are traditionally conjugated to carrier proteins possessing T-cell epitope peptides, such as tetanus toxoid (TT), bovine serum albumin (BSA), and OVA, to enhance the presentation of carbohydrate antigens to the immune system and improve the immunogenicity of vaccines. , Recently, chemical, enzymatic, and chemoenzymatic synthesis as well as engineered biosynthesis of oligosaccharides have been explored to boost the development of carbohydrate-based vaccines. ,− …”

Section: Immunologymentioning

confidence: 99%

Carbohydrate-Based Macromolecular Biomaterials

et al. 2021

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Carbohydrates are the most abundant and one of the most important biomacromolecules in Nature. Except for energy-related compounds, carbohydrates can be roughly divided into two categories: Carbohydrates as matter and carbohydrates as information. As matter, carbohydrates are abundantly present in the extracellular matrix of animals and cell walls of various plants, bacteria, fungi, etc., serving as scaffolds. Some commonly found polysaccharides are featured as biocompatible materials with controllable rigidity and functionality, forming polymeric biomaterials which are widely used in drug delivery, tissue engineering, etc. As information, carbohydrates are usually referred to the glycans from glycoproteins, glycolipids, and proteoglycans, which bind to proteins or other carbohydrates, thereby meditating the cell–cell and cell–matrix interactions. These glycans could be simplified as synthetic glycopolymers, glycolipids, and glycoproteins, which could be afforded through polymerization, multistep synthesis, or a semisynthetic strategy. The information role of carbohydrates can be demonstrated not only as targeting reagents but also as immune antigens and adjuvants. The latter are also included in this review as they are always in a macromolecular formulation. In this review, we intend to provide a relatively comprehensive summary of carbohydrate-based macromolecular biomaterials since 2010 while emphasizing the fundamental understanding to guide the rational design of biomaterials. Carbohydrate-based macromolecules on the basis of their resources and chemical structures will be discussed, including naturally occurring polysaccharides, naturally derived synthetic polysaccharides, glycopolymers/glycodendrimers, supramolecular glycopolymers, and synthetic glycolipids/glycoproteins. Multiscale structure–function relationships in several major application areas, including delivery systems, tissue engineering, and immunology, will be detailed. We hope this review will provide valuable information for the development of carbohydrate-based macromolecular biomaterials and build a bridge between the carbohydrates as matter and the carbohydrates as information to promote new biomaterial design in the near future.

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Engineering a new generation of carbohydrate-based vaccines

Cited by 15 publications

References 73 publications

Carbohydrate Conjugates in Vaccine Developments

Carbohydrate Conjugates in Vaccine Developments

Synthesis and delivery ofStreptococcus pneumoniaecapsular polysaccharides by recombinant attenuatedSalmonellavaccines

Carbohydrate-Based Macromolecular Biomaterials

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