Yuhui Wang ¹ Yuhan Di ^1* Jingliang Qin ^2* Yanling Wang ^2* Yuhui Wang ¹ Juan Wang ^3* Haining Tan ^1*

• ¹ Shandong University, Jinan, China
• ² Nankai University, Tianjin, China
• ³ Jinan Maternity And Child Care Hospital, Jinan, Shandong Province, China

Glycoconjugate vaccines are an important class of efficacious and safe commercial vaccines and have led to a significant reduction in the global occurrence of drug-resistant bacterial infections. Glycoconjugate vaccines are synthesized by covalently linking bacterial polysaccharide antigens to a carrier protein. Given the stronger and longer-lasting immune response than a pure polysaccharide activating with B cells alone, glycoconjugate vaccines have become one of the promising vaccine types.However, the chemical synthesis of glycoconjugate vaccines is complex, costly, and laborious, and thus the efficient preparation of biosynthetic glycoconjugates using microbial cell factory has emerged as a highly desirable manufacturing alternative. This review focuses on advancements in the recombinant microbial biosynthesis of glycoconjugate vaccines and summarizes various strategies to optimize their production. It is based on three key aspects: the selection of oligosaccharyltransferases, the use of different vaccine carrier proteins, and the enhancement of key concentrations in the UDP-sugar supply. Finally, the review highlights technical challenges and discusses future directions for recombinantly synthesized glycoconjugate vaccines.