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Mechanism of Antigen Presentation and Specificity of Antibody Cross-Reactivity Elicited by an Oligosaccharide-Conjugate Cancer Vaccine

[Image: see text] Polysaccharides have been successfully used as immunogens for the development of vaccines against bacterial infection; however, there are no oligosaccharide-based vaccines available to date and no previous studies of their processing and presentation. We reported here the intracell...

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Detalles Bibliográficos
Autores principales: Wang, Szu-Wen, Ko, Yi-An, Chen, Chiang-Yun, Liao, Kuo-Shiang, Chang, Yi-Hsuan, Lee, Hsin-Yu, Yu, Yueh-Hsiang, Lih, Yu-Hsuan, Cheng, Yang-Yu, Lin, Heng-Hsin, Hsu, Tsui-Ling, Wu, Chung-Yi, Lin, Kuo-I, Wong, Chi-Huey
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2023
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10161213/
https://www.ncbi.nlm.nih.gov/pubmed/37089019
http://dx.doi.org/10.1021/jacs.3c02003
Descripción
Sumario:[Image: see text] Polysaccharides have been successfully used as immunogens for the development of vaccines against bacterial infection; however, there are no oligosaccharide-based vaccines available to date and no previous studies of their processing and presentation. We reported here the intracellular enzymatic processing and antigen presentation of an oligosaccharide-conjugate cancer vaccine prepared from the glycan of Globo-H (GH), a globo-series glycosphingolipid (GSL). This oligosaccharide-conjugate vaccine was shown to elicit antibodies against the glycan moieties of all three globo-series GSLs that are exclusively expressed on many types of cancer and their stem cells. To understand the specificity and origin of cross-reactivity of the antibodies elicited by the vaccine, we found that the vaccine is first processed by fucosidase 1 in the early endosome of dendritic cells to generate a common glycan antigen of the GSLs along with GH for MHC class II presentation. This work represents the first study of oligosaccharide processing and presentation and is expected to facilitate the design and development of glycoconjugate vaccines based on oligosaccharide antigens.