Estudo preliminar da estabilidade de conjugados de PRP-TT em tampão fosfato

Abstract

The bacterium Haemophilus is responsible for causing several diseases of clinical relevance, among its several species, Haemophilus influenzae serotype b (Hib), the most prevalent serotype, stands out for causing serious infections in children up to 5 years old. One of the most serious diseases caused by it is meningitis, responsible for severe sequelae such as permanent brain damage, hearing loss, among others, and depending on the state of health of the child can lead to death. One of the most effective ways of reducing the disease is through vaccination. The polyribosyl ribitol phosphate (PRP) capsule is the main virulence factor; however, a vaccine composed only of the capsular polysaccharide is not capable of inducing a protective immune response in children under two years old, so it is necessary to conjugate it to a carrier protein. The available commercial anti-Hib vaccine is composed by PRP conjugated to tetanus toxoid. Our laboratory has been studying the synthesis of conjugates of capsular polysaccharides to proteins. Among the various stages of vaccine development, stability testing is required. The main objective of the present work is to evaluate the stability of previously synthesized PRP-TT conjugates stored in phosphate buffer solution (Na2HPO4 50 mM, NaCl 150 mM, 0.005% Thimerosal) at 40C. Samples will be analyzed by Size Exclusion Liquid Chromatography (SEC) and the polysaccharide content determined by colorimetric method.