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2. Carbohydrate Conjugates in Vaccine Developments

Author

Shuyao Lang and Xuefei Huang

Subjects
adjuvant, carbohydrates, immune activation, vaccine development, glyco-conjugates, Chemistry, QD1-999
Abstract

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.

Published
2020
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3. Chemoenzymatic Synthesis of 9NHAc-GD2 Antigen to Overcome the Hydrolytic Instability of O-Acetylated-GD2 for Anticancer Conjugate Vaccine Development

Author

Paulo Vilar Saavedra, Herbert W. Kavunja, Xuanjun Wu, Jinfeng Ye, Shuyao Lang, Tayeb Kakeshpour, Jeffrey C. Gildersleeve, Hongzhi Cao, Yuetao Zhao, Vilma Yuzbasiyan-Gurkan, Zahra Rashidijahanabad, Sherif Ramadan, Andrew T DeLaitsch, and Xuefei Huang

Subjects
Cancer Vaccines, Catalysis, Article, chemistry.chemical_compound, Mice, Antigen, Conjugate vaccine, Gangliosides, Neuraminic acid, Acetamides, Vaccine Development, Carbohydrate Conformation, Animals, Ganglioside, Vaccines, Conjugate, biology, Chemistry, Immunogenicity, Hydrolysis, Acetylation, General Chemistry, Biochemistry, Immunization, biology.protein, Neuraminic Acids, Antibody, Conjugate
Abstract

Ganglioside GD2 is an attractive tumor-associated carbohydrate antigen for anti-cancer vaccine development. However, its low immunogenicity and the significant side effects observed with anti-GD2 antibodies present significant obstacles for vaccines. To overcome these, a new GD2 derivative bearing an N-acetamide (NHAc) at its non-reducing end neuraminic acid (9NHAc-GD2) has been designed to mimic the 9-O-acetylated-GD2 (9OAc-GD2), a GD2 based antigen with a restricted expression on tumor cells. 9NHAc-GD2 was synthesized efficiently via a chemoenzymatic method and subsequently conjugated with a powerful carrier bacteriophage Qβ. Mouse immunization with the Qβ-9NHAc-GD2 conjugate elicited strong and long-lasting IgG antibodies, which were highly selective toward 9NHAc-GD2 with little cross-recognition of GD2. Immunization of canines with Qβ-9NHAc-GD2 showed the construct was immunogenic in canines with little adverse effects, paving the way for future clinical translation to humans.

Published
2021

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