A comprehensive synthetic library of poly-N-acetyl glucosamines enabled vaccine against lethal challenges of Staphylococcus aureus

Zibin Tan; Weizhun Yang; Nicholas A. O’Brien; Xingling Pan; Sherif Ramadan; Terence Marsh; Neal Hammer; Colette Cywes-Bentley; Mariana Vinacur; Gerald B. Pier; Jeffrey C. Gildersleeve; Xuefei Huang

doi:10.1038/s41467-024-47457-4

Nature Communications (Apr 2024)

A comprehensive synthetic library of poly-N-acetyl glucosamines enabled vaccine against lethal challenges of Staphylococcus aureus

Zibin Tan,
Weizhun Yang,
Nicholas A. O’Brien,
Xingling Pan,
Sherif Ramadan,
Terence Marsh,
Neal Hammer,
Colette Cywes-Bentley,
Mariana Vinacur,
Gerald B. Pier,
Jeffrey C. Gildersleeve,
Xuefei Huang

Affiliations

Zibin Tan: Department of Chemistry, Michigan State University
Weizhun Yang: Department of Chemistry, Michigan State University
Nicholas A. O’Brien: Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute
Xingling Pan: Department of Chemistry, Michigan State University
Sherif Ramadan: Department of Chemistry, Michigan State University
Terence Marsh: Department of Microbiology, Genetics & Immunology, Michigan State University
Neal Hammer: Department of Microbiology, Genetics & Immunology, Michigan State University
Colette Cywes-Bentley: Division of Infectious Diseases, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School
Mariana Vinacur: Division of Infectious Diseases, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School
Gerald B. Pier: Division of Infectious Diseases, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School
Jeffrey C. Gildersleeve: Chemical Biology Laboratory, Center for Cancer Research, National Cancer Institute
Xuefei Huang: Department of Chemistry, Michigan State University

DOI: https://doi.org/10.1038/s41467-024-47457-4
Journal volume & issue: Vol. 15, no. 1
pp. 1 – 16

Abstract

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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.

Published in Nature Communications

ISSN: 2041-1723 (Online)
Publisher: Nature Portfolio
Country of publisher: United Kingdom
LCC subjects: Science
Website: https://www.nature.com/ncomms/

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