RESUMEN
5-Azido-3-oxa-pentyl beta-D-galactopyranoside was prepared from diethylene glycol monochlorohydrin and used as a model of oligosaccharide hapten. After deprotection, a series of amides bearing thiophilic groups had been obtained through the terminal amino function and essayed in coupling reactions with thiolated BSA. Also several Lewis human blood group oligosaccharides had been conjugated with thiolated BSA demonstrating the usefulness of the methodology.
Asunto(s)
Glicósidos/química , Proteínas/química , Compuestos de Sulfhidrilo/química , Conformación de Carbohidratos , Secuencia de Carbohidratos , Humanos , Espectroscopía de Resonancia Magnética , Datos de Secuencia MolecularRESUMEN
Polysaccharide-protein conjugates as vaccines have proven to be very effective in preventing Haemophilus influenzae type b infections in industrialized countries. However, cost-effective technologies need to be developed for increasing the availability of anti-H. influenzae type b vaccines in countries from the developing world. Consequently, vaccine production with partially synthetic antigens is a desirable goal for many reasons. They may be rigidly controlled for purity and effectiveness while at the same time being cheap enough that they may be made universally available. We describe here the antigenicity and immunogenicity of several H. influenzae type b synthetic oligosaccharide-protein conjugates in laboratory animals. The serum of H. influenzae type b-immunized animals recognized our synthetic H. influenzae type b antigens to the same extent as the native bacterial capsular polysaccharide. Compared to the anti-H. influenzae type b vaccine employed, these synthetic versions induced similar antibody response patterns in terms of titer, specificity, and functional capacity. The further development of synthetic vaccines will meet urgent needs in the less prosperous parts of the world and remains our major goal.
Asunto(s)
Vacunas contra Haemophilus/inmunología , Haemophilus influenzae tipo b/inmunología , Oligosacáridos/inmunología , Pentosafosfatos/inmunología , Polisacáridos Bacterianos/inmunología , Vacunas Sintéticas/inmunología , Animales , Anticuerpos Antibacterianos/inmunología , Femenino , Ratones , Ratones Endogámicos BALB C , Conejos , Ratas , Ratas Sprague-Dawley , Vacunas Conjugadas/inmunologíaRESUMEN
Glycoconjugate vaccines provide effective prophylaxis against bacterial infections. To date, however, no commercial vaccine has been available in which the key carbohydrate antigens are produced synthetically. We describe the large-scale synthesis, pharmaceutical development, and clinical evaluation of a conjugate vaccine composed of a synthetic capsular polysaccharide antigen of Haemophilus influenzae type b (Hib). The vaccine was evaluated in clinical trials in Cuba and showed long-term protective antibody titers that compared favorably to licensed products prepared with the Hib polysaccharide extracted from bacteria. This demonstrates that access to synthetic complex carbohydrate-based vaccines is feasible and provides a basis for further development of similar approaches for other human pathogens.