A Comprehensive Synthetic Library of Poly-N-acetyl Glucosamines Enabled Vaccine Against Lethal Challenges of Staphylococcus Aureus

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Apr 24

PMID 38658531

Authors

Zibin Tan

Weizhun Yang

Nicholas A OBrien

Xingling Pan

Sherif Ramadan

Terence Marsh

Neal Hammer

Colette Cywes-Bentley

Mariana Vinacur

Gerald B Pier

Jeffrey C Gildersleeve

Xuefei Huang

Affiliations

Soon will be listed here.

Abstract

Poly-β-(1-6)-N-acetylglucosamine (PNAG) is an important vaccine target, expressed on many pathogens. A critical hurdle in developing PNAG based vaccine is that the impacts of the number and the position of free amine vs N-acetylation on its antigenicity are not well understood. In this work, a divergent strategy is developed to synthesize a comprehensive library of 32 PNAG pentasaccharides. This library enables the identification of PNAG sequences with specific patterns of free amines as epitopes for vaccines against Staphylococcus aureus (S. aureus), an important human pathogen. Active vaccination with the conjugate of discovered PNAG epitope with mutant bacteriophage Qβ as a vaccine carrier as well as passive vaccination with diluted rabbit antisera provides mice with near complete protection against infections by S. aureus including methicillin-resistant S. aureus (MRSA). Thus, the comprehensive PNAG pentasaccharide library is an exciting tool to empower the design of next generation vaccines.

Citing Articles

Targeting -Acetylglucosaminidase in with Iminosugar Inhibitors.

Sluga J, Tomasic T, Anderluh M, Hrast Rambaher M, Bajc G, Sevsek A Antibiotics (Basel). 2024; 13(8).

PMID: 39200051 PMC: 11350809. DOI: 10.3390/antibiotics13080751.

Inducing Long Lasting B Cell and T Cell Immunity Against Multiple Variants of SARS-CoV-2 Through Mutant Bacteriophage Qβ-Receptor Binding Domain Conjugate.

Tan Z, Yang C, Lin P, Ramadan S, Yang W, Rashidi Z Adv Healthc Mater. 2024; 13(20):e2302755.

PMID: 38733291 PMC: 11305917. DOI: 10.1002/adhm.202302755.

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