A LIQUID STABLE BIOLOGICAL ACTIVE SEMI-SYNTHETIC GLYCOCONJUGATE VACCINE AGAINST HAEMOPHILUS INFLUENZAE TYPE b

摘要

Haemophilus influenzae type b (Hib) is a causative organism of childhood pneumoniae and meningitis [1]. Commercial licensed glycoconjugate vaccines against Hib save the lives of millions of children in both developing and developed countries [2]. The major issue with Hib glycoconjugate vaccines is lack of stability of Hib polysaccharides in the presence of water and adjuvants [3]. Phosphodiester bonds present in the polyribosylribitol phosphate of the Hib capsular polysaccharide undergo significant cleavage or migration in the presence of an adjuvant like aluminum hydroxide. To overcome this problem, we rationally designed and synthesized oligosaccharide analogs of the Hib capsular polysaccharide. These novel oligosaccharides were stable at temperatures up to 70 °C when tested in water and formulations containing adjuvants. Hib analogs were conjugated to the carrier protein CRM197 and tested for their immune response in rabbits. HiberiX~R served as a positive control. The synthetic Hib oligosaccharide analog in liquid formulation with-/without aluminum hydroxide showed antibody titers comparable to the commercial vaccine HiberiX~R over three administration study. A booster dose with the same vaccine batch administered after a 12-week resting period elicited antibody titers comparable to the commercial vaccine HiberiX~R indicating prolonged stability of the Hib analog containing glycoconjugate vaccine.