Development of synthetic carbohydrate-based antibacterial vaccines against Gram-negative bacteria

Professor Li, Xuechen   (Principal Investigator (PI))

Professor Chen Sheng   (Co-Investigator)

33

2021-12-01

1361000

Development of synthetic carbohydrate-based antibacterial vaccines against Gram-negative bacteria

antibacterial vaccine, carrier protein, glycoconjugate, pseudaminic acid, synthetic carbohydrate

Others - Medicine, Dentistry and Health

Physical Sciences (P)

20190802

Health and Medical Research Fund - Full Grant

2020

On-going

Objectives: to develop synthetic carbohydrate-based antibacterial vaccines against Gram-negative bacteria, with an aim to offer an alternative strategy to protect us from infectious infections and combat bacterial multidrug resistance. Hypothesis to be tested: bacterial pseudaminic acid (Pse) glycans are distributed in numerous pathogenic bacteria as components of cell surface-associated glycans. Pse is unique to the Gram-negative bacteria and is structurally very distinct from other mammalian carbohydrates. Thus, we hypothesize that development of Pse-based vaccine is a promising strategy against pathogens with Pse present on the surface. Design and Subjects: We will use chemical synthesis to prepare homogeneous Pse and its derivatives, and then conjugate them with the carrier proteins. Thus-obtained Pse glycoconjugates will be evaluated for their potentials to elicit the antibody and protect animal models from bacterial infection. Instruments: LCMS, HPLC, PFLC, NMR, high speed centrifuges, ultracentrifuge, selectrophoresis setup and animal facilities Main outcome measures: Development of effective antibacterial vaccine candidate for further advancement. Data processing and analysis: All results are presented as group means with standard deviation. Statistical analysis will be performed using analysis of variance (ANOVA). Significance is accepted when the p-value is <0.05. Expected results: Pse glycans are very unique to the Gram-negative pathogens. The success of this application will generate new and promising Pse-based antibacterial vaccine candidate for the further therapeutic development.