Chemical Synthesis and Immunological Evaluation of a Pentasaccharide Bearing Multiple Rare Sugars as a Potential Anti‐pertussis Vaccine. Issue 16 (25th February 2020)

• Record Type: Journal Article
• Authors: Wang, Peng; Huo, Chang‐xin; Lang, Shuyao; Caution, Kyle; Nick, Setare Tahmasebi; Dubey, Purnima; Deora, Rajendar; Huang, Xuefei
• Is Part Of: Angewandte Chemie international edition. Volume 59:Issue 16(2020)
• Page Start: 6451
• Page End: 6458
• Publication Date: 2020-02-25
• Subjects: bacteriophage Qβ -- lipo-oligosaccharides -- pertussis -- synthesis -- vaccines; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201915913
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: With the infection rate of Bordetella pertussis at a 60‐year high, there is an urgent need for new anti‐pertussis vaccines. The lipopolysaccharide (LPS) of B. pertussis is an attractive antigen for vaccine development. With the presence of multiple rare sugars and unusual glycosyl linkages, the B. pertussis LPS is a highly challenging synthetic target. In this work, aided by molecular dynamics simulation and modeling, a pertussis‐LPS‐like pentasaccharide was chemically synthesized for the first time. The pentasaccharide was conjugated with a powerful carrier, bacteriophage Qβ, as a vaccine candidate. Immunization of mice with the conjugate induced robust anti‐glycan IgG responses with IgG titers reaching several million enzyme‐linked immunosorbent assay (ELISA) units. The antibodies generated were long lasting and boostable and could recognize multiple clinical strains of B. pertussis, highlighting the potential of Qβ‐glycan as a new anti‐pertussis vaccine. Abstract : A pertussis‐liposaccharide (LPS)‐like pentasaccharide bearing multiple rare sugar subunits was synthesized with high stereoselectivity and overall yield. Conjugation of the pentasaccharide with the carrier protein Qβ yielded a vaccine candidate, which induced anti‐LPS antibodies in mice with broad‐spectrum recognitions for B. pertussis strains.