Chemical Synthesis and Immunological Evaluation of a Pentasaccharide Bearing Multiple Rare Sugars as a Potential Anti-pertussis Vaccine |
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Authors: | Dr. Peng Wang Dr. Chang-xin Huo Shuyao Lang Dr. Kyle Caution Dr. Setare Tahmasebi Nick Prof. Purnima Dubey Prof. Rajendar Deora Prof. Xuefei Huang |
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Affiliation: | 1. Department of Chemistry, Michigan State University, 578 South Shaw Lane, East Lansing, MI, 48824 USA;2. Department of Microbial Infection and Immunity, The Ohio State University, 460 W 12th Ave, Columbus, OH, 43210 USA |
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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. |
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Keywords: | Bakteriophage Qβ Impfstoffe Lipo-Oligosaccharide Pertussis Synthese |
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