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Tesi etd-12052022-191136


Tipo di tesi
Tesi di laurea magistrale LM5
Autore
SANTOSTEFANO, GIOVANNI
URN
etd-12052022-191136
Titolo
Synthesis of Haemophilus Influenzae type b (Hib) capsular polysaccharide analogues
Dipartimento
FARMACIA
Corso di studi
CHIMICA E TECNOLOGIA FARMACEUTICHE
Relatori
relatore Prof.ssa Di Bussolo, Valeria
relatore Dott.ssa Del Bino, Linda
relatore Dott.ssa Romano, Maria Rosaria
Parole chiave
  • glyco-immunology
  • glycoconjugate vaccines
  • Haemophilus Influenzae
  • synthetic approach
Data inizio appello
18/01/2023
Consultabilità
Non consultabile
Data di rilascio
18/01/2093
Riassunto
In the last decade glyco-immunology, the research field dealing with the specific interactions of carbohydrates with the immune system, acquired a growing interest. The oligo- and polysaccharides that cover the cell surface of bacterial pathogens are crucial virulence factors being capable to interact with the immune system inducing the production of carbohydrate specific antibodies. For this reason, they represent an attractive target for vaccine design, especially for glycoconjugate vaccines that are the product of chemical linkage between carbohydrate antigen and a carrier protein. Since the first ever conjugate vaccine in 1987 against Haemophilus Influenzae type B (Hib) was licensed, a lot of glycoconjugate vaccines have been developed. These are among the safest and most successful vaccines developed during the past 30 years and are part of routine vaccinations in many countries. New technologies like bioconjugation and solid-phase oligosaccharide synthesis have been developed but still today the main process used for conjugate vaccines production is the semi-synthetic approach starting from bacterial fermentation. In fact, despite the enormous progress achieved by the medicinal and carbohydrate chemistry research, the completely synthetic glycoconjugate vaccine production is still today a big challenge because of manufacturing costs and process complexity compared to natural polysaccharides extraction.Actually, Quimi-Hib (Cuba, 2004) is the only fully synthetic glycoconjugate vaccine approved for human use and it is composed of a synthetic mimic of Hib capsular polysaccharide conjugated to TT. Quimi-Hib makes part of a list of licensed glycoconjugate vaccines against Haemophilus
Influenzae serotype B (Hib), a bacterium that still today causes severe diseases including meningitis, pneumonia, and septicemia, especially in infants and children. The latter are more vulnerable due to an undeveloped immune system, which makes them the most in need of new improved and efficacious vaccines. Other synthetic vaccines (Shigella Flexneri type 2a synthetic O-antigen conjugated to TT; dPNAG pentamer conjugated to TT) have been tested in clinical trials. As well as avoiding the need to handle pathogens, synthetic glycoconjugates offer clear advantages in terms of product characterization and the possibility to understand the parameters influencing immunogenicity.
In this master thesis work we present a synthetic approach to the preparation of oligosaccharide antigen for vaccines design.
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