Ramesh K. Sood

Capsular polysaccharide-protein conjugate vaccines

The conjugation of polysaccharides to carrier proteins generally enhances polysaccharide immunogenicity and renders the immune response T-cell dependent. Such enhancement of immunogenicity has made the use of conjugate vaccines possible in populations that are otherwise unresponsive to polysaccharide vaccines. Here, the authors discuss the value of capsular polysaccharide vaccines, their ability to elicit protective immunity against infectious bacteria, the selection of appropriate polysaccharides and carrier proteins, and the applications of the resultant conjugate vaccines.

Novel ring-expanded nucleoside analogs exhibit potent and selective inhibition of hepatitis B virus replication in cultured human hepatoblastoma cells

Novel ring-expanded nucleoside (REN) analogs (1-3) containing 5:7 fused ring systems as the heterocyclic base were found to be potent and selective inhibitors of hepatitis B virus (HBV) replication in cultured human hepatoblastoma 2.2.15 cells. The most active compound, 6-amino-4,5-dihydro-8H-1-(beta-D-ribofuranosyl)imidazo[4,5-e][1,3]diazepine-4,8-dione (1), inhibited the synthesis of intracellular HBV replication intermediates and extracellular virion release in 2.2.15 cells with 50% effective concentration (EC50) of 0.604 and 0.131 microM, respectively. All three compounds had no effect on the synthesis of viral ribonucleic acids (RNA) in 2.2.15 cells. These compounds also exhibited low cellular toxicity in stationary and rapidly growing cell systems.

Capsular polysaccharide-protein conjugate vaccines and intravenous immunoglobulins.

Capsular polysaccharides (CPs), present on the surface of most pathogenic bacteria, have been recognised as virulence factors. Antibodies specific to these polysaccharides can mediate the killing of these bacteria by phagocytes in the presence of complement. The conjugation of polysaccharides to carrier proteins enhances their immunogenicity and renders the immune response T-cell dependent. The currently licensed capsular polysaccharide vaccines and polysaccharide-protein conjugate vaccines under development for the prevention of bacterial infections will be discussed in this review. Use of these vaccines for active vaccination and for the vaccination of healthy plasma donors to produce hyperimmune iv. immunoglobulins for the passive immunisation of appropriate patient populations is also discussed.

6-Amino-1-(2’-deoxy-b-D-ribofuranosyl)-4,5-dihydro-8H-imidazo[4,5-e][1,3]diazepine-4,8-dione

The starting methyl 1-(2’-deoxy-b-D-ribofuranosyl)imidazole-4,5-dicarboxylate (1) was prepared by deoxygenation of the corresponding riboside, employing the literature procedure [1].[...]