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 and Xuefei Huang ()
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Zibin Tan: Michigan State University
Weizhun Yang: Michigan State University
Nicholas A. O’Brien: National Cancer Institute
Xingling Pan: Michigan State University
Sherif Ramadan: Michigan State University
Terence Marsh: Michigan State University
Neal Hammer: Michigan State University
Colette Cywes-Bentley: Harvard Medical School
Mariana Vinacur: Harvard Medical School
Gerald B. Pier: Harvard Medical School
Jeffrey C. Gildersleeve: National Cancer Institute
Xuefei Huang: Michigan State University

Nature Communications, 2024, vol. 15, issue 1, 1-16

Abstract: 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.

Date: 2024
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DOI: 10.1038/s41467-024-47457-4

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