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.

Synthetic Studies on the Incorporation of N-Acetylallosamine in Hyaluronic Acid-Inspired Thiodisaccharides

“…Furthermore, this enzyme has been associated to certain asthmatic and allergic conditions [ 15 ] and anti-asthmatic activity was reported for allosamidin in a mouse model of asthma [ 16 ]. This result reinforces the importance of exploring non-classical carbohydrate structures as candidates for therapeutic purposes, and thus focusing efforts on developing convenient synthetic pathways [ 17 , 18 ]. It should also be mentioned that many antibiotics are composed of deoxy amino monosaccharides and carbasugars, which are considered rare sugars as well.…”

Recent advances on smart glycoconjugate vaccines in infections and cancer

“…Despite the fact that to date, the expression of biosynthetic pathways and glycoengineering to produce bacterial glycans provides cheaper and versatile method to develop carbohydrates vaccines [94], recent advances in carbohydrate synthesis allowed access to many complex oligosaccharides on a large scale and with precise control of the structure [44]. Synthetic strategies aimed at the development of conjugate vaccines containing protein/peptide carriers are mainly based on the incorporation of either a synthetic bacterial carbohydrate antigen [95][96][97][98][99][100][101][102][103][104][105], their synthetic structural mimics, or chimeric oligosaccharides [11]. Relevant examples of the latter approach were reported during the last decade.…”

Synthesis of L‐Hexoses: An Update

“…Kulkarni and co‐workers pioneered the regioselective displacement of 2,4‐bistriflates of hexopyranoses to access a variety of rare, bacterial D‐ and L‐deoxy amino sugars in an expedient way [70] . These developments have greatly helped synthesis of a variety of bacterial glycoconjugates [71–74] . The other popular method to access rare deoxy amino L‐hexoses is azido nitration/selenation of L‐fucal or L‐rhamnal [75,76] .…”

“…[70] These developments have greatly helped synthesis of a variety of bacterial glycoconjugates. [71][72][73][74] The other popular method to access rare deoxy amino L-hexoses is azido nitration/selenation of L-fucal or L-rhamnal. [75,76] The progress in the synthesis of rare sugars containing bacterial glycoconjugates has been recently reviewed.…”