期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 59, 期 16, 页码 6451-6458出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201915913
关键词
bacteriophage Q beta; lipo-oligosaccharides; pertussis; synthesis; vaccines
资金
- National Institute of Allergy and Infectious Diseases, NIH [R01AI146210, R01AI125560]
- National Cancer Institute, NIH [R01CA225105]
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 Q beta, 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 Q beta-glycan as a new anti-pertussis vaccine.
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