Semisynthetic Glycoconjugates as Potential Vaccine Candidates Against Haemophilus influenzae Type a.

Autor: Kohout CV; Department of Chemistry, Università degli Studi di Milano, Milano, Italy., Del Bino L; GSK, Research Centre, Siena, Italy., Petrosilli L; Department of Chemistry, Università degli Studi di Milano, Milano, Italy., D'Orazio G; Department of Chemistry, Università degli Studi di Milano, Milano, Italy., Romano MR; GSK, Research Centre, Siena, Italy., Codée JDC; Leiden Institute of Chemistry, Leiden University, Leiden, Netherlands., Adamo R; GSK, Research Centre, Siena, Italy., Lay L; Department of Chemistry, Università degli Studi di Milano, Milano, Italy.
Jazyk: angličtina
Zdroj: Chemistry (Weinheim an der Bergstrasse, Germany) [Chemistry] 2024 Aug 22; Vol. 30 (47), pp. e202401695. Date of Electronic Publication: 2024 Jul 30.
DOI: 10.1002/chem.202401695
Abstrakt: Glycoconjugate vaccines are based on chemical conjugation of pathogen-associated carbohydrates with immunogenic carrier proteins and are considered a very cost-effective way to prevent infections. Most of the licensed glycoconjugate vaccines are composed of saccharide antigens extracted from bacterial sources. However, synthetic oligosaccharide antigens have become a promising alternative to natural polysaccharides with the advantage of being well-defined structures providing homogeneous conjugates. Haemophilus influenzae (Hi) is responsible for a number of severe diseases. In recent years, an increasing rate of invasive infections caused by Hi serotype a (Hia) raised some concern, because no vaccine targeting Hia is currently available. The capsular polysaccharide (CPS) of Hia is constituted by phosphodiester-linked 4-β-d-glucose-(1→4)-d-ribitol-5-(PO 4 →) repeating units and is the antigen for protein-conjugated polysaccharide vaccines. To investigate the antigenic potential of the CPS from Hia, we synthesized related saccharide fragments containing up to five repeating units. Following the synthetic optimization of the needed disaccharide building blocks, they were assembled using the phosphoramidite approach for the installation of the phosphodiester linkages. The resulting CPS-based Hia oligomers were conjugated to CRM 197 carrier protein and evaluated in vivo for their immunogenic potential, showing that all glycoconjugates were capable of raising antibodies recognizing Hia synthetic fragments.
(© 2024 Wiley-VCH GmbH.)
Databáze: MEDLINE
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