18 results on '"Xiu-Jing Zheng"'
Search Results
2. Synthesis and Immunological Evaluation of Pentamannose-Based HIV-1 Vaccine Candidates
- Author
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Chang-Cheng Liu, Chang-Xin Huo, Canjia Zhai, Xiu-Jing Zheng, De-Cai Xiong, and Xin-Shan Ye
- Subjects
Pharmacology ,Vaccines ,Organic Chemistry ,Biomedical Engineering ,Pharmaceutical Science ,Bioengineering ,HIV Antibodies ,HIV Envelope Protein gp120 ,Antibodies, Neutralizing ,Epitopes ,Mice ,Polysaccharides ,HIV-1 ,Animals ,Humans ,Glycoconjugates ,Biotechnology - Abstract
Dense glycosylation and the trimeric conformation of the human immunodeficiency virus-1 (HIV-1) envelope protein limit the accessibility of some cellular glycan processing enzymes and end up with high-mannose-type
- Published
- 2022
3. Synthesis and immunological evaluation of N-acyl modified Globo H derivatives as anticancer vaccine candidates
- Author
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Chengcheng Song, Xiu-Jing Zheng, Xin-Shan Ye, and Canjia Zhai
- Subjects
Synthetic vaccine ,Glycosylation ,Glycoconjugate ,medicine.medical_treatment ,Pharmaceutical Science ,H antigen ,010402 general chemistry ,01 natural sciences ,Biochemistry ,chemistry.chemical_compound ,Immune system ,Drug Discovery ,medicine ,Pharmacology ,chemistry.chemical_classification ,biology ,010405 organic chemistry ,Immunogenicity ,Organic Chemistry ,0104 chemical sciences ,chemistry ,Cancer research ,biology.protein ,Molecular Medicine ,Antibody ,Adjuvant - Abstract
Globo H is a tumor-associated carbohydrate antigen (TACA), which serves as a valuable target for antitumor vaccine or cancer immunotherapies. However, most TACAs are T-cell-independent, and they cannot induce powerful immune response due to their poor immunogenicity. To address this problem, herein, several Globo H analogues with modification on the N-acyl group were prepared through a preactivation-based glycosylation strategy from the non-reducing end to the reducing end. These modified Globo H derivatives were then conjugated with carrier protein CRM197 to form glycoconjugates as anticancer vaccine candidates, which were used in combination with adjuvant glycolipid C34 for immunological studies. The immunological effects of these synthetic vaccine candidates were evaluated on Balb/c mice. The results showed that the fluorine-modified N-acyl Globo H conjugates can induce higher titers of IgG antibodies that can recognize the naturally occurring Globo H antigen on the surface of cancer cells and can eliminate cancer cells in the presence of a complement, indicating the potential of these synthetic glycoconjugates as anticancer vaccine candidates.
- Published
- 2021
4. Synthesis and immunological evaluation of
- Author
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Canjia, Zhai, Xiu-Jing, Zheng, Chengcheng, Song, and Xin-Shan, Ye
- Subjects
Chemistry - Abstract
Globo H is a tumor-associated carbohydrate antigen (TACA), which serves as a valuable target for antitumor vaccine or cancer immunotherapies. However, most TACAs are T-cell-independent, and they cannot induce powerful immune response due to their poor immunogenicity. To address this problem, herein, several Globo H analogues with modification on the N-acyl group were prepared through a preactivation-based glycosylation strategy from the non-reducing end to the reducing end. These modified Globo H derivatives were then conjugated with carrier protein CRM197 to form glycoconjugates as anticancer vaccine candidates, which were used in combination with adjuvant glycolipid C34 for immunological studies. The immunological effects of these synthetic vaccine candidates were evaluated on Balb/c mice. The results showed that the fluorine-modified N-acyl Globo H conjugates can induce higher titers of IgG antibodies that can recognize the naturally occurring Globo H antigen on the surface of cancer cells and can eliminate cancer cells in the presence of a complement, indicating the potential of these synthetic glycoconjugates as anticancer vaccine candidates.
- Published
- 2021
5. Chemical synthesis and biological evaluation of penta- to octa- saccharide fragments of Vi polysaccharide fromSalmonella typhi
- Author
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Meng-Man Wei, Xin-Shan Ye, Gao-Lan Zhang, De-Cai Xiong, Yu-Feng Ma, Chengcheng Song, and Xiu-Jing Zheng
- Subjects
chemistry.chemical_classification ,010405 organic chemistry ,Chemistry ,Pentamer ,Organic Chemistry ,Glycoside ,Oligosaccharide ,010402 general chemistry ,Salmonella typhi ,Polysaccharide ,01 natural sciences ,Chemical synthesis ,Epitope ,0104 chemical sciences ,Biochemistry ,Conjugate vaccine - Abstract
Vi antigen is the capsular polysaccharide of Salmonella typhi, which can cause typhoid fever. With the increasing threat of antiboitic resistance, vaccination against Salmonella typhi is a preferred way to prevent this disease. Chemical synthesis of fragments of Vi antigen is in urgent need for the development of structure-homogeneous and quality-controlled oligosaccharide vaccines. However, it is extremely challenging to synthesize large oligosaccharide fragments of Vi antigen owing to the exclusive α-1,4-linkage of polyaminogalacturonates. Herein, a series of Vi oligosaccharides ranging from pentamer to octamer were efficiently prepared using 2,3-N,O-oxazolidinone protected glycosides as building blocks based on the preactivation protocol. The heptasaccharide and octasaccharide fragments were synthesized for the first time. The competitive ELISA evaluation suggested that the hexasaccharide might be the minimum epitope of Vi antigen, which provides a significant guidance for the future development of Vi oligosaccharide vaccines.
- Published
- 2018
6. A cancer vaccine based on fluorine-modified sialyl-Tn induces robust immune responses in a murine model
- Author
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Chengcheng Song, Chang-Cheng Liu, Xiu-Jing Zheng, Yifa Zhou, and Xin-Shan Ye
- Subjects
Cytotoxicity, Immunologic ,0301 basic medicine ,glycoconjugate vaccine ,medicine.medical_treatment ,tumor-associated carbohydrate antigen ,chemical and pharmacologic phenomena ,complex mixtures ,Cancer Vaccines ,Immune tolerance ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Adjuvants, Immunologic ,Cancer immunotherapy ,Antigen ,T-Lymphocyte Subsets ,Cell Line, Tumor ,Neoplasms ,medicine ,Animals ,Antigens, Tumor-Associated, Carbohydrate ,cross reaction ,Immunity, Cellular ,cancer immunotherapy ,business.industry ,Immunogenicity ,Antibody-Dependent Cell Cytotoxicity ,Immunity ,hemic and immune systems ,Fluorine ,Immunotherapy ,Disease Models, Animal ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Antibody Formation ,Immunology ,Female ,Immunization ,Cancer vaccine ,fluoro-substituted STn ,business ,therapeutics ,Adjuvant ,Research Paper - Abstract
// Chengcheng Song 1, 2 , Xiu-Jing Zheng 1 , Chang-Cheng Liu 1 , Yifa Zhou 2 and Xin-Shan Ye 1 1 State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China 2 School of Life Sciences, Northeast Normal University, Changchun 130024, China Correspondence to: Xin-Shan Ye, email: xinshan@bjmu.edu.cn Yifa Zhou, email: zhouyf383@nenu.edu.cn Keywords: cancer immunotherapy, glycoconjugate vaccine, tumor-associated carbohydrate antigen, fluoro-substituted STn, cross reaction Received: March 08, 2017 Accepted: April 19, 2017 Published: May 07, 2017 ABSTRACT Development of an effective vaccine to target tumor associated carbohydrate antigens, aberrantly expressed on the cell surface of various carcinomas, is an appealing approach toward cancer immunotherapy. However, a major problem of carbohydrate antigens is their poor immunogenicity. Immunization with modified-carbohydrate antigens could improve the immunogenicity and induce cross reaction with the native carbohydrate antigens. In this study, we investigated the antitumor ability of three fluoro-substituted sialyl-Tn (STn) analogues (2, 3, 4) coupled to KLH (keyhole limpet hemocyanin) and studied the mechanism of tumor immunotherapy of the vaccines in a murine model of colon cancer. Vaccination with 4-KLH, in which the two N -acetyl groups of STn are substituted with N -fluoroacetyl groups, could remarkably prolong the survival of tumor-bearing mouse and resulted in a significant reduction in tumor burden of lungs compared with STn-KLH (1-KLH). The vaccine 4-KLH could provoke stronger cytotoxic T lymphocytes immune response, T helper (Th) cell-mediated immune response and an earlier-stage Th1 immune response than 1-KLH, thus breaking immune tolerance and generating a therapeutic response. The 4-KLH vaccine induced strong tumor-specific anti-STn antibodies which could mediate complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity against human tumor cells. Moreover, in the absence of adjuvant, 4-KLH still elicited stronger immune responses than 1-KLH. Our data suggested that 4-KLH is superior in tumor prevention. The strategic hapten fluorination may be a potential approach applicable to the vaccines development for the cancer immunotherapy.
- Published
- 2017
7. Fluorine-modified sialyl-Tn-CRM197 vaccine elicits a robust immune response
- Author
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Xin-Shan Ye, Yifa Zhou, Haili Guo, Fan Zhang, Qin Li, Chengcheng Song, Xiu-Jing Zheng, and Yafei Cao
- Subjects
Halogenation ,Antibodies, Neoplasm ,medicine.medical_treatment ,Gene Expression ,Lymphocyte proliferation ,Biochemistry ,Mice ,Immunogenicity, Vaccine ,Cancer immunotherapy ,Lymphocytes ,Th1-Th2 Balance ,Antibody-dependent cell-mediated cytotoxicity ,0303 health sciences ,Immunity, Cellular ,Mice, Inbred BALB C ,Chemistry ,Immunogenicity ,030302 biochemistry & molecular biology ,surgical procedures, operative ,Colonic Neoplasms ,Female ,therapeutics ,Adjuvant ,Cancer Vaccines ,03 medical and health sciences ,Interferon-gamma ,Immune system ,Antigen ,Adjuvants, Immunologic ,Bacterial Proteins ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Antigens, Tumor-Associated, Carbohydrate ,Molecular Biology ,030304 developmental biology ,Immune Sera ,Antibody-Dependent Cell Cytotoxicity ,Cell Biology ,nervous system diseases ,Immunity, Humoral ,nervous system ,Humoral immunity ,Cancer research ,Immunization ,sense organs ,Interleukin-4 ,Glycoconjugates ,Spleen - Abstract
Even though a vaccine that targets tumor-associated carbohydrate antigens on epithelial carcinoma cells presents an attractive therapeutic approach, relatively poor immunogenicity limits its development. In this study, we investigated the immunological activity of a fluoro-substituted Sialyl-Tn (F-STn) analogue coupled to the non-toxic cross-reactive material of diphtheria toxin197 (CRM197). Our results indicate that F-STn-CRM197 promotes a greater immunogenicity than non-fluorinated STn-CRM197. In the presence or absence of adjuvant, F-STn-CRM197 remarkably enhances both cellular and humoral immunity against STn by increasing antigen-specific lymphocyte proliferation and inducing a mixed Th1/Th2 response leading to production of IFN-γ and IL-4 cytokines, as well as STn-specific antibodies. Furthermore, antisera produced from F-STn-CRM197 immunization significantly recognizes STn-positive tumor cells and increases cancer cell lysis induced by antibody-dependent cell-mediated cytotoxicity (ADCC) or complement-dependent cytotoxicity (CDC) pathways. Our data suggest that this F-STn vaccine may be useful for cancer immunotherapy and possibly for prophylactic prevention of cancer.
- Published
- 2019
8. Altering the Specificity of the Antibody Response to HIV gp120 with a Glycoconjugate Antigen
- Author
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Canjia Zhai, Xin-Shan Ye, Chang-Cheng Liu, and Xiu-Jing Zheng
- Subjects
0301 basic medicine ,Glycan ,Glycoconjugate ,Oligosaccharides ,HIV Antibodies ,HIV Envelope Protein gp120 ,01 natural sciences ,Biochemistry ,Epitope ,Mannans ,Affinity maturation ,Epitopes ,03 medical and health sciences ,Antigen ,Animals ,Antigens ,AIDS Vaccines ,chemistry.chemical_classification ,Mice, Inbred BALB C ,Vaccines, Synthetic ,biology ,010405 organic chemistry ,Antibodies, Monoclonal ,Serum Albumin, Bovine ,General Medicine ,HIV envelope protein ,Antibodies, Neutralizing ,Virology ,0104 chemical sciences ,030104 developmental biology ,Immunization ,chemistry ,Antibody Formation ,Immunology ,biology.protein ,Molecular Medicine ,Cattle ,Female ,Antibody ,Glycoconjugates ,Broadly Neutralizing Antibodies - Abstract
Some conserved glycans on the HIV envelope protein are targets of broadly neutralizing antibodies (bnAbs) of HIV. BnAbs provide a precise definition of broadly neutralizing epitopes on the envelope protein of HIV. These epitopes are promising for vaccine design. Many glycan-related antigens with high affinity to bnAbs have been tested as immunogens in vivo. However, it was found that no bnAb-like antibodies were induced. Vaccination with different immunogens containing the same neutralizing epitope may enhance the affinity maturation of antibodies which focus on the shared epitope. This combined immunization strategy showed great potential in peptide epitope-based vaccine design. However, it has not yet been explored on glycan-related epitopes to date. Herein, we take 2G12 as a model to validate this strategy on glycan-related epitopes. A high-affinity antigen of 2G12 was constructed by conjugating the D1 arm tetramannoside to bovine serum albumin. Then, the glycoconjugate was coimmunized with a recombinant gp120, which was expected to selectively benefit the induction of antibodies recognizing the neutralizing epitope of 2G12 on gp120. Mice were inoculated with the two antigens simultaneously or alternately to determine the suitable regimen for this strategy. The serological assays demonstrated that the antibody titers and subtypes responded to the whole gp120 were not improved, and the proportion of antibodies competitively bound to the 2G12 epitope was not enhanced significantly either. However, the coimmunized glycoconjugate selectively raised the proportion of antibodies recognizing D1 arm tetramannoside-related structures on gp120. These results provide important experience for the design of glycan-dependent bnAb-based vaccines.
- Published
- 2016
9. Synthesis and immunological evaluation of MUC1 glycopeptide conjugates bearing N-acetyl modified STn derivatives as anticancer vaccines
- Author
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Chengcheng Song, Xiu-Jing Zheng, An Xiao, Xin-Shan Ye, Yue Gui, and Chang-Xin Huo
- Subjects
Synthetic vaccine ,010402 general chemistry ,Cancer Vaccines ,digestive system ,01 natural sciences ,Biochemistry ,Mice ,Antigen ,Cell Line, Tumor ,Neoplasms ,Animals ,Humans ,Antigens, Tumor-Associated, Carbohydrate ,Physical and Theoretical Chemistry ,skin and connective tissue diseases ,neoplasms ,MUC1 ,chemistry.chemical_classification ,Mice, Inbred BALB C ,biology ,010405 organic chemistry ,Chemistry ,Immune Sera ,Immunogenicity ,Mucin-1 ,Organic Chemistry ,Glycopeptides ,digestive system diseases ,biological factors ,Glycopeptide ,0104 chemical sciences ,Hemocyanins ,biology.protein ,Female ,Immunization ,Antibody ,Glycoprotein ,Keyhole limpet hemocyanin - Abstract
Glycoprotein MUC1 is an attractive target for anti-tumor vaccine development. However, the weak immunogenicity of MUC1 remains a significant problem. To solve this problem, several STn derivatives with N-acetyl modifications were synthesized and incorporated into a 20-amino acid MUC1 tandem repeat sequence. The modified STn-MUC1 glycopeptides were further connected to a carrier protein keyhole limpet hemocyanin (KLH). The immunological effects of these synthetic vaccine conjugates were evaluated using the BALB/c mouse model. The results showed that vaccine V2 elicited higher titers of antibodies which cross-reacted with the native STn-MUC1 antigen. Moreover, the elicited antisera reacted with the STn-MUC1 antigen-positive tumor cells, indicating that the carbohydrate antigen modification strategy may hold potential to overcome the weak immunogenicity of natural MUC1 glycopeptides.
- Published
- 2016
10. Synthetic and immunological studies of N-acyl modified S-linked STn derivatives as anticancer vaccine candidates
- Author
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Chang-Cheng Liu, Xiu-Jing Zheng, Xin-Shan Ye, An Xiao, Chang-Xin Huo, Shuang Sun, and Zhuo Lv
- Subjects
Male ,chemistry.chemical_classification ,Mice, Inbred BALB C ,Glycan ,biology ,Glycoconjugate ,Carbohydrate chemistry ,Immunogenicity ,Organic Chemistry ,Cancer Vaccines ,Biochemistry ,Antigen ,chemistry ,biology.protein ,Animals ,Antigens, Tumor-Associated, Carbohydrate ,Female ,Immunization ,Physical and Theoretical Chemistry ,Antibody ,Glycoconjugates ,Keyhole limpet hemocyanin ,Conjugate - Abstract
It is well known that tumor cells express some aberrant glycans, termed tumor-associated carbohydrate antigens (TACAs). TACAs are good targets for the development of carbohydrate-based anticancer vaccines. However, one of the major problems is that carbohydrate antigens possess a weak immunogenicity. To tackle this problem, a number of unnatural N-modified S-linked STn analogues were designed and prepared. Reaction of the modified STn disaccharides with bifunctional adipic acid p-nitrophenyl diester provided the corresponding activated esters, which was followed by the conjugation with keyhole limpet hemocyanin (KLH), affording the corresponding protein conjugates. The immunological properties of these glycoconjugates were evaluated in a mouse model. The results showed that the modified glycoconjugates stimulated the production of IgG antibodies that are capable of recognizing the naturally occurring STn antigen, helping the discovery of carbohydrate-based anticancer vaccine candidates.
- Published
- 2015
11. Correction: Synthesis and immunological evaluation of MUC1 glycopeptide conjugates bearing N-acetyl modified STn derivatives as anticancer vaccines
- Author
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Chengcheng Song, Xin-Shan Ye, Xiu-Jing Zheng, Chang-Xin Huo, An Xiao, and Yue Gui
- Subjects
Chemistry ,Organic Chemistry ,Physical and Theoretical Chemistry ,Biochemistry ,Combinatorial chemistry ,MUC1 ,Glycopeptide ,Conjugate - Abstract
Correction for ‘Synthesis and immunological evaluation of MUC1 glycopeptide conjugates bearing N-acetyl modified STn derivatives as anticancer vaccines’ by An Xiao et al., Org. Biomol. Chem., 2016, 14, 7226–7237.
- Published
- 2017
12. ChemInform Abstract: Broadly Neutralizing Antibody-Guided Carbohydrate-Based HIV Vaccine Design: Challenges and Opportunities
- Author
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Chang-Cheng Liu, Xiu-Jing Zheng, and Xin-Shan Ye
- Subjects
Affinity maturation ,Antigenicity ,Chronic infection ,Immune system ,Immunization ,biology ,Antigen ,Chemistry ,biology.protein ,General Medicine ,HIV vaccine ,Antibody ,Virology - Abstract
The HIV envelope (Env) is heavily glycosylated, facilitating the spread and survival of HIV in many ways. Some potent broadly neutralizing antibodies (bnAbs) such as 2G12, PG9, PG16, and PGTs can recognize the conserved glycan residues on Env. The bnAbs, which often emerge after many years of chronic infection, provide insight into the vulnerability of HIV and can therefore guide the design of vaccines. Many carbohydrate-conjugated vaccines have been designed to induce bnAb-like antibodies, but none have yet been successful. The low antigenicity of these vaccines is one possible explanation. New strategies have been applied to obtain high-affinity antigens of glycan-dependent and other bnAbs. However, when used as immunogens in vivo, high-affinity antigens are still insufficient in eliciting bnAb-like antibodies. bnAbs generally possess some unusual features and may therefore be suppressed by the host immune system. In view of this situation, some immunization regimens based on the affinity maturation of antibodies have been tested. Herein we summarize recent studies into the design of carbohydrate-based HIV vaccines and some valuable experiences gained in work with other bnAb-based HIV vaccines.
- Published
- 2016
13. Synthesis and Evaluation of Glycoconjugates Comprising N-Acyl-Modified Thomsen-Friedenreich Antigens as Anticancer Vaccines
- Author
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Chengcheng Song, Xin-Shan Ye, Shuang Sun, Xiu-Jing Zheng, Chang-Xin Huo, and Qin Li
- Subjects
Cellular immunity ,Glycoconjugate ,Cell Survival ,Lymphocyte ,Biology ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Cancer Vaccines ,Cell Line ,Mice ,Antigen ,Bacterial Proteins ,Drug Discovery ,medicine ,Animals ,Antigens, Tumor-Associated, Carbohydrate ,Lymphocytes ,General Pharmacology, Toxicology and Pharmaceutics ,Pharmacology ,chemistry.chemical_classification ,Antiserum ,Diphtheria toxin ,Mice, Inbred BALB C ,010405 organic chemistry ,Immunogenicity ,Organic Chemistry ,Molecular biology ,0104 chemical sciences ,medicine.anatomical_structure ,chemistry ,Immunoglobulin G ,biology.protein ,Molecular Medicine ,Female ,Antibody ,Glycoconjugates - Abstract
Thomsen-Friedenreich (TF) antigen is an important tumor-associated carbohydrate antigen. Its low immunogenicity, however, limits its application in the development of anticancer vaccines. To solve this problem, several N-acyl-modified TF derivatives were synthesized and conjugated with carrier protein CRM197 (a mutated diphtheria toxoid cross-reactive material). The immunological results in BALB/c mice demonstrated that these modified TF antigen conjugates could stimulate the production of higher titers of IgG antibodies that cross-reacted with native TF antigen. These glycoconjugates showed strong lymphocyte proliferative response, suggesting that they can induce cellular immunity. Furthermore, the elicited antisera reacted strongly with TF-positive tumor cells (4T1). In particular, the N-monofluoroacetyl-modified TF conjugate 4-CRM197 showed the strongest complement-dependent cytotoxicity effect against 4T1 cells, implying the potential of this glycoconjugate as an anticancer vaccine.
- Published
- 2016
14. Broadly Neutralizing Antibody-Guided Carbohydrate-Based HIV Vaccine Design: Challenges and Opportunities
- Author
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Xin-Shan Ye, Chang-Cheng Liu, and Xiu-Jing Zheng
- Subjects
0301 basic medicine ,Antigenicity ,Antibody Affinity ,HIV Infections ,Biology ,010402 general chemistry ,01 natural sciences ,Biochemistry ,Affinity maturation ,03 medical and health sciences ,Immune system ,Antigen ,Drug Discovery ,Animals ,Humans ,General Pharmacology, Toxicology and Pharmaceutics ,HIV vaccine ,Pharmacology ,AIDS Vaccines ,Organic Chemistry ,Vaccination ,env Gene Products, Human Immunodeficiency Virus ,Virology ,Antibodies, Neutralizing ,0104 chemical sciences ,030104 developmental biology ,Immunization ,Immunology ,HIV-1 ,Molecular Medicine ,Glycoconjugates - Abstract
The HIV envelope (Env) is heavily glycosylated, facilitating the spread and survival of HIV in many ways. Some potent broadly neutralizing antibodies (bnAbs) such as 2G12, PG9, PG16, and PGTs can recognize the conserved glycan residues on Env. The bnAbs, which often emerge after many years of chronic infection, provide insight into the vulnerability of HIV and can therefore guide the design of vaccines. Many carbohydrate-conjugated vaccines have been designed to induce bnAb-like antibodies, but none have yet been successful. The low antigenicity of these vaccines is one possible explanation. New strategies have been applied to obtain high-affinity antigens of glycan-dependent and other bnAbs. However, when used as immunogens in vivo, high-affinity antigens are still insufficient in eliciting bnAb-like antibodies. bnAbs generally possess some unusual features and may therefore be suppressed by the host immune system. In view of this situation, some immunization regimens based on the affinity maturation of antibodies have been tested. Herein we summarize recent studies into the design of carbohydrate-based HIV vaccines and some valuable experiences gained in work with other bnAb-based HIV vaccines.
- Published
- 2015
15. Enhancement of the Immunogenicity of Synthetic Carbohydrate Vaccines by Chemical Modifications of STn Antigen
- Author
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Ye Zhang, Yue Wang, Chang-Xin Huo, Xin-Shan Ye, Xiu-Jing Zheng, and Fan Yang
- Subjects
Glycan ,Synthetic antigen ,Carbohydrates ,Enzyme-Linked Immunosorbent Assay ,Cancer Vaccines ,Biochemistry ,Mice ,Antigen ,Carbohydrate Conformation ,Animals ,Antigens, Tumor-Associated, Carbohydrate ,Antiserum ,Mice, Inbred BALB C ,Vaccines, Synthetic ,biology ,Immunogenicity ,Vaccination ,Stereoisomerism ,General Medicine ,Virology ,In vitro ,nervous system diseases ,Titer ,surgical procedures, operative ,Immunoglobulin M ,nervous system ,Immunoglobulin G ,Immunology ,biology.protein ,Molecular Medicine ,Female - Abstract
The abnormal glycans expressed on the surface of tumor cells, known as tumor-associated carbohydrate antigens, increase the chance to develop carbohydrate-based anticancer vaccines. However, carbohydrate antigens pose certain difficulties, and the major drawback is their weak immunogenicity. To tackle this problem, numerous structurally modified STn antigens were designed and synthesized in this work. These synthetic antigens were screened in vitro by using competitive ELISA method, and the antigens with positive response were conjugated to the protein carrier for vaccination. The vaccination results on mice showed that some fluorine-containing modifications on the STn antigen can significantly increase the anti-STn IgG titers and improve the ratios of anti-STn IgG/IgM. The antisera can recognize the tumor cells expressing the native STn antigen.
- Published
- 2011
16. Improvement of the immune efficacy of carbohydrate vaccines by chemical modification on the GM3 antigen
- Author
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Fan Yang, Xin-Shan Ye, Ye Zhang, Mingwei Zheng, Xiu-Jing Zheng, and Chang-Xin Huo
- Subjects
endocrine system ,Glycosylation ,Glycoconjugate ,medicine.medical_treatment ,Molecular Conformation ,Biochemistry ,Antigen-Antibody Reactions ,chemistry.chemical_compound ,Immune system ,Cancer immunotherapy ,Antigen ,medicine ,G(M3) Ganglioside ,Physical and Theoretical Chemistry ,Antigens ,chemistry.chemical_classification ,Vaccines ,biology ,Chemistry ,Immunogenicity ,Organic Chemistry ,Virology ,carbohydrates (lipids) ,Vaccination ,Immunology ,biology.protein ,lipids (amino acids, peptides, and proteins) ,Antibody - Abstract
Tumor cells often display aberrant levels and patterns of cell surface glycosylation, which provides a potential opportunity to develop carbohydrate-based anticancer vaccines for cancer immunotherapy. However, one of the most addressed challenges in this field is the low efficiency of the carbohydrate vaccination due to poor immunogenicity of carbohydrate antigens. In this article, a number of structure-modified GM3 antigen analogues were designed and chemically synthesized. The modified GM3 antigens were conjugated to protein carriers for vaccination. The vaccination results on mice show that the modification on the GM3 antigen could improve the efficiency of the vaccination, and in particular, two glycoconjugates (3-KLH and 8-KLH) elicited higher titers of anti-GM3 antibodies than the unmodified GM3-protein conjugate (2-KLH) did.
- Published
- 2015
17. A highly α-stereoselective synthesis of oligosaccharide fragments of the Vi antigen from Salmonella typhi and their antigenic activities
- Author
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Lin Yang, Xin-Shan Ye, Xiu-Jing Zheng, Jingjing Zhu, and Guihua Tai
- Subjects
chemistry.chemical_classification ,Glycosylation ,Molecular Structure ,Chemistry ,Organic Chemistry ,Polysaccharides, Bacterial ,Glycoside ,General Chemistry ,Oligosaccharide ,Salmonella typhi ,Polysaccharide ,Catalysis ,chemistry.chemical_compound ,Structure-Activity Relationship ,Antigen ,Biochemistry ,Carbohydrate Sequence ,Tetrasaccharide ,Structure–activity relationship - Abstract
In this paper, a convenient approach to the synthesis of the repeating α-(1→4)-linked N-acetyl galactosaminuronic acid units from the capsular polysaccharide of Salmonella typhi is reported. The exclusively α-stereoselective glycosylation reactions were achieved by using oxazolidinone-protected glycosides as building blocks based on a pre-activation protocol. Di-, tri-, and tetrasaccharides were prepared by this short and efficient approach in high yields. The enzyme-linked immunosorbent assay experiments show that our synthetic tri- and tetrasaccharide had much higher antigenic activities than previously reported ones in the inhibition of antibody binding by the native polysaccharide. The results demonstrate that the antigenic activities of saccharides can be strengthened greatly by increasing the number of acetyl groups present.
- Published
- 2011
18. Design and syntheses of some iminosugar derivatives as potential immunosuppressants
- Author
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Xin-Shan Ye, Lihe Zhang, Guo-Liang Zhang, and Xiu-Jing Zheng
- Subjects
Pharmacology ,Chemistry ,Stereochemistry ,Drug Discovery ,Organic Chemistry ,Iminosugar ,Pharmaceutical Science ,Molecular Medicine ,Epimer ,Biochemistry ,Combinatorial chemistry ,IC50 - Abstract
Eleven new iminosugar derivatives were synthesized and the effects of these synthetic iminosugars on proliferation of the mouse splenocytes were evaluated by the cell counting kit-8 (CCK-8) assay. The preliminary structure–activity relationships were deduced from the experimental data. It was found that iminosugar 14 (IC50 = 22 μM) and its C-5 epimer 15 (IC50 = 45 μM) displayed the strongest inhibitory effects, and might hold potential as immunosuppressive agents.
- Published
- 2011
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