A Bioactive Synthetic Outer‐Core Oligosaccharide Derived from a Klebsiella pneumonia Lipopolysaccharide for Bacteria Recognition

Abstract

There is an urgent need for new treatment options for carbapenem-resistant Klebsiella pneumoniae (K. pneumoniae), which is a common cause of life-threatening hospitaland community-acquired infections. Prophylactic or therapeutic vaccination may offer an approach to control these infections, however, none has yet been approved for human use. Here, we report the chemical synthesis of an outer core tetra-and pentasaccharide derived from the lipopolysaccharide of K. pneumoniae. The oligosaccharides were equipped with an aminopentyl linker, which facilitated conjugation to the carrier proteins CRM 197 and BSA. Mice immunized with the glycoconjugate vaccine candidates elicited antibodies that recognized isolated LPS as well as various strains of K. pneumoniae. The successful preparation of the oligosaccharides relied on the selection of monosaccharide building blocks equipped with orthogonal hydroxyl and amino protecting groups. It allowed the differentiation of three types of amines of the target compounds and the installation of a crowded 4,5-branched Kdo moiety.

A heptavalent O-antigen bioconjugate vaccine exhibits differential functional antibody responses against diverseKlebsiella pneumoniaeisolates

“…In addition to capsule, the components of LPS have also been considered for vaccine inclusion. Conjugate vaccines linking segments of LPS (other than the O-antigen) to a protein have been described (37, 38). These vaccines elicited antibodies; however, only one group demonstrated protection from a lethal K. pneumoniae challenge.…”

Serum antibody screening using glycan arrays

“…171 Arrays have also been used to study responses to Chlamydia pneumoniae vaccines. 154,155,173 4.1.4 Bacterial glycan-binding proteins and infectioninduced autoantibodies. Interestingly, the fimbriae of bacteria possess adhesins that enable the bacteria to bind to glycans and mediate disease.…”

Multifunctional Lipidated Protein Carrier with a Built-In Adjuvant as a Universal Vaccine Platform Potently Elevates Immunogenicity of Weak Antigens

“…It is worth noting that the N -terminal amino acid of BSA is aspartic acid, which has a very high conversion efficiency in PLP-mediated transamination reactions . Additionally, previous research has indicated that as carrier proteins, BSA and cross-reacting material 197 (CRM197) have a similar enhancement effect on the immunogenicity of haptens . In the vaccine design, the resulting Pam 3 CSK 4 –BSA-MUC1 lipoprotein was subsequently incorporated into liposomes, which biomimics the membrane structure of tumor cells and facilitates the multivalent presentation for immune response augmentation.…”