Sialyl-Tn Polysaccharide A1 as an Entirely Carbohydrate Immunogen: Synthesis and Immunological Evaluation

Shi, Mengchao; Kleski, Kristopher A.; Trabbic, Kevin R.; Bourgault, Jean‐Paul; Andreana, Peter R.

doi:10.1021/jacs.6b05675

Cited by 52 publications

(55 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A high level of IL-17A, a pro-inflammatory factor promoting CD4 + T cell proliferation, was detected in anti-Tn-PS A1 sera but not in anti-PS A1 sera. Besides Tn antigen, other TACAs such as sialyl-Tn (STn) (Nishat and Andreana, 2016;Shi et al, 2016) and Thomsen-Friedenreich (Tf) (Trabbic et al, 2016) have been conjugated with PS A1 (Scheme 1B) and another ZPS, i.e., PS B (Scheme 1C) (Trabbic et al, 2016). The conjugates were able to induce moderate levels of both IgM and IgG antibodies against the target TACAs.…”

Section: Zwitterionic Polysaccharides (Zpss)mentioning

confidence: 99%

Carbohydrate Conjugates in Vaccine Developments

Lang

Huang

2020

Front. Chem.

View full text Add to dashboard Cite

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.

show abstract

Section: Zwitterionic Polysaccharides (Zpss)mentioning

confidence: 99%

Carbohydrate Conjugates in Vaccine Developments

Lang

Huang

2020

Front. Chem.

View full text Add to dashboard Cite

show abstract

“…An estimated percent loading can be obtained from the proton spectra of Tn-PS A1 (4a), TF-PS A1 (4b), and Tn-TF-PS A1 (4c) by integration of the N-acetyl peaks. Although this method may introduce potential error due to peak overlap, we have demonstrated this method previously [17,43]. Based on the integration of N-acetyl peaks, percent loadings were calculated to be 13% for Tn-PS A1 (4a), 19% for TF-PS A1 (4b), and a combined loading of 18% for Tn-TF-PS A1 (4c) ( Table S1).…”

Section: Synthesis and Characterization Of Taca-ps A1 Conjugatesmentioning

confidence: 99%

“…Specificity was also supported by data presented in Figure S4 where the stimulation of anti-Tn-PS A1 splenocytes with TF-PS A1 did not increase IL-17 production. IFN-γ is a canonical cytokine produced by Th1 cells, and the amount of IFN-γ producing cells in an ELISpot assay can provide insight into T cell activation [17,56,57]. Displayed in Figure S5, anti-Tn-TF-PS A1 splenocytes were able to generate increased levels of IFN-γ producing cells than anti-TF-PS A1 splenocytes when both were co-cultured with TF-PS A1.…”

Section: Quantification Of Cytokine Producing Cells With Elispotmentioning

confidence: 99%

“…PS A1 is a zwitterionic polysaccharide (ZPS) isolated from the commensal bacteria Bacteroides fragilis (ATCC 25285/NCTC 9343) capable of activating CD4+ T cells in a major histocompatibility complex-II (MHC-II) dependent mechanism [20,21]. PS A1 is an effective immunogenic carrier for TACAs and is evidenced by our previous work with Tn-PS A1 and STn-PS A1 [17,18,22]. These PS A1 conjugates were able to induce protective immune responses that consisted of potent antibody production, cellular immunity, and the production of proinflammatory markers such as T helper 17 (Th17) cells and IL-17, which are essential in the protection against cancer [23,24].…”

Section: Introductionmentioning

confidence: 96%

“…Our research efforts focus on the issues of developing carbohydrate specific immunity by utilizing a semi-synthetic entirely carbohydrate vaccine platform. This two-component platform consists of an anomeric aminooxy TACA derivative conjugated to Polysaccharide A1 (PS A1) via oxime bond and has been demonstrated with the TF antigen, the Thomsen-nouveau (Tn, α-d-GalNAcp) antigen, and the sialyl-Tn (STn, α-d-Neu5Ac-(2,6)-α-d-GalNAcp) antigen [17][18][19]. PS A1 is a zwitterionic polysaccharide (ZPS) isolated from the commensal bacteria Bacteroides fragilis (ATCC 25285/NCTC 9343) capable of activating CD4+ T cells in a major histocompatibility complex-II (MHC-II) dependent mechanism [20,21].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Enhanced Immune Response Against the Thomsen-Friedenreich Tumor Antigen Using a Bivalent Entirely Carbohydrate Conjugate

et al. 2020

Self Cite

View full text Add to dashboard Cite

The Thomsen-Friedenreich (TF) antigen is a key target for the development of anticancer vaccines, and this ongoing challenge remains relevant due to the poor immunogenicity of the TF antigen. To overcome this challenge, we adopted a bivalent conjugate design which introduced both the TF antigen and the Thomsen-nouveau (Tn) antigen onto the immunologically relevant polysaccharide A1 (PS A1). The immunological results in C57BL/6 mice revealed that the bivalent, Tn-TF-PS A1 conjugate increased the immune response towards the TF antigen as compared to the monovalent TF-PS A1. This phenomenon was first observed with enzyme-linked immunosorbent assay (ELISA) where the bivalent conjugate generated high titers of IgG antibodies where the monovalent conjugate generated an exclusive IgM response. Fluorescence-activated cell sorting (FACS) analysis also revealed increased binding events to the tumor cell lines MCF-7 and OVCAR-5, which are consistent with the enhanced tumor cell lysis observed in a complement dependent cytotoxicity (CDC) assay. The cytokine profile generated by the bivalent construct revealed increased pro-inflammatory cytokines IL-17 and IFN-γ. This increase in cytokine concentration was matched with an increase in cytokine producing cells as observed by ELISpot. We hypothesized the mechanisms for this phenomenon to involve the macrophage galactose N-acetylgalactosamine specific lectin 2 (MGL2). This hypothesis was supported by using biotinylated probes and recombinant MGL2 to measure carbohydrate-protein interactions.

show abstract

Syntheses of α(2,8) Sialosides Containing NeuAc and NeuGc by Using Double Carbonyl‐Protected N‐Acyl Sialyl Donors

Takeuchi,

Tohda,

Tanaka

2024

Chemistry A European J

View full text Add to dashboard Cite

We report on the syntheses of NeuAc and NeuGc‐containing glycosides via the use of double carbonyl‐protected N‐acetyl sialyl donors. The 7‐O,9‐O‐carbonyl protection of an N‐acyl‐5‐N,4‐O‐carbonyl‐protected sialyl donor markedly increased the a‐selectivity during glycosylation, particularly when glycosylating the C‐8 hydroxyl group of sialic acids. The N‐acyl carbamates were selectively opened with ethanethiol under basic conditions to provide N‐acyl amines. It is noteworthy that N‐glycolyl carbamate was more reactive to nucleophiles by comparison with the N‐acetyl carbamate due to the electron‐withdrawing oxygen in the N‐acyl group and however, allowed selective opening of the carbamates without the loss of N‐glycolyl groups. To demonstrate the utility of the approach, we began by synthesizing α(2,3) and α(2,6) sialyl galactosides. Glycosylation of the hydroxy groups of galactosides at the C‐6 position with the NeuAc and NeuGc donors provided the corresponding sialyl galactoses in good yields with excellent a‐selectivity. However, glycosylation of the 2,3‐diol galactosyl acceptor selectively provided Siaα(2,2)Gal. Next, we prepared a series of α(2,8) disialosides composed of NeuAc and NeuGc. Glycosylation of NeuGc and NeuAc acceptors at the C‐8 hydroxyl group with NeuGc and NeuAc sialyl donors provided the corresponding α(2,8) disialosides, and no significant differences were detected in the reactivities of these acceptors.

show abstract

Sialyl-Tn Polysaccharide A1 as an Entirely Carbohydrate Immunogen: Synthesis and Immunological Evaluation

Cited by 52 publications

References 88 publications

Carbohydrate Conjugates in Vaccine Developments

Carbohydrate Conjugates in Vaccine Developments

Enhanced Immune Response Against the Thomsen-Friedenreich Tumor Antigen Using a Bivalent Entirely Carbohydrate Conjugate

Syntheses of α(2,8) Sialosides Containing NeuAc and NeuGc by Using Double Carbonyl‐Protected N‐Acyl Sialyl Donors

Contact Info

Product

Resources

About