Chemical Synthesis and Immunological Evaluation of a Pentasaccharide Bearing Multiple Rare Sugars as a Potential Anti‐pertussis Vaccine

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.

Chemoenzymatic Synthesis of 9NHAc‐GD2 Antigen to Overcome the Hydrolytic Instability of O‐Acetylated‐GD2 for Anticancer Conjugate Vaccine Development

“…[26] Furthermore,s ubstitutions of OAcw ith NHAc did not significantly impact the native interactions between the sialoglycans and their protein receptors. [26] Fort he induction of strong and long-lasting antibody responses,iti sc ritical that the GD2 antigen is conjugated to an immunogenic carrier.Bacteriophage Qb virus-like particle (VLP), apowerful carrier for tumor associated carbohydrate antigens, [27][28][29] was investigated in GD2 based vaccine design. Thea mine groups of GD2 1 and 9NHAc-GD2 3 were converted to thiocyanate GD2 11 and 9NHAc-GD2 12 with thiophosgene [30] (Scheme 4), which were then added to bacteriophage Qb virus-like particles in K-Phos buffer (0.1 M, pH 8) overnight at 37 8 8Ct og ive Qb-GD2 conjugate Angewandte Chemie 13 and Qb-9NHAc-GD2 conjugate 14 (Scheme 5a).…”

Chemoenzymatic Synthesis of 9NHAc‐GD2 Antigen to Overcome the Hydrolytic Instability of O‐Acetylated‐GD2 for Anticancer Conjugate Vaccine Development

“…[26] Furthermore,s ubstitutions of OAcw ith NHAc did not significantly impact the native interactions between the sialoglycans and their protein receptors. [26] Fort he induction of strong and long-lasting antibody responses,iti sc ritical that the GD2 antigen is conjugated to an immunogenic carrier.Bacteriophage Qb virus-like particle (VLP), apowerful carrier for tumor associated carbohydrate antigens, [27][28][29] was investigated in GD2 based vaccine design. Thea mine groups of GD2 1 and 9NHAc-GD2 3 were converted to thiocyanate GD2 11 and 9NHAc-GD2 12 with thiophosgene [30] (Scheme 4), which were then added to bacteriophage Qb virus-like particles in K-Phos buffer (0.1 M, pH 8) overnight at 37 8 8Ct og ive Qb-GD2 conjugate…”

Recent Advances in Stereocontrolled Mannosylation: Focus on Glycans Comprising Acidic and/or Amino Sugars

“…Although these glycosylations proceeded stereoselectively and the reduction of the oximino group to 2‐acetamido‐2‐deoxy‐ β ‐D‐mannuronate was carried out to afford the desired ManNAcA derivatives in good yields, this approach found much more scarce application than in the synthesis of ManNAc glycosides described in the previous section. 1,2‐ cis ‐Linked 2,3‐diamino mannuronic acid residues are also found on several bacterial polysaccharides and only few reports have been published on their synthesis [66,125–126] …”