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The development of a vaccine for tuberculosis requires a combination of antigens and adjuvants capable of inducing appropriate and long-lasting T cell immunity. We evaluated Mtb72F formulated in AS02A in the cynomolgus monkey model. The vaccine was immunogenic and caused no adverse reactions. When monkeys were immunized with bacillus Calmette–Guérin (BCG) and then boosted with Mtb72F in AS02A, protection superior to that afforded by using BCG alone was achieved, as measured by clinical parameters, pathology, and survival. We observed long-term survival and evidence of reversal of disease progression in monkeys immunized with the prime-boost regimen. Antigen-specific responses from protected monkeys receiving BCG and Mtb72F/AS02A had a distinctive cytokine profile characterized by an increased ratio between 3 Th1 cytokines, IFN-γ, TNF, and IL-2 and an innate cytokine, IL-6. To our knowledge, this is an initial report of a vaccine capable of inducing long-term protection against tuberculosis in a nonhuman primate model, as determined by protection against severe disease and death, and by other clinical and histopathological parameters.

Evidence is presented suggesting that hepatocytes contain a receptor that binds glycoproteins specifically through fucose in al-..3 linkage to N-acetylglucosamine. Human After the initial observations of Ashwell and coworkers (1, 2) that mammalian hepatocytes contain a protein that specifically binds asialoglycoproteins through exposed galactose residues, several other animal binding proteins were reported. A (3-galactoside binding protein has been described from calf heart and lung (3), chick embryo thigh muscle (4), and the electric organ of Electrophorus electricus (5), but they have properties that differ somewhat from the hepatocyte protein and perhaps from one another. Avian liver also contains a protein that binds glycoproteins with exposed N-acetylglucosamine (6), and considerable evidence has been reported for mannose-specific binding proteins (7).This report provides evidence suggesting the presence of a receptor in hepatocytes that specifically binds oligosaccharides in glycoproteins through a fucosyl al-3 N-acetylglucosamine group. These studies were prompted by the observations that human lactoferrin (Lf) was rapidly cleared from the circulation when injected intravenously in rats and mice, and that over 90% of the injected protein was recovered in hepatocytes.The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement " in accordance with 18 U. S. C. §1734 solely to indicate this fact.Much is known about Lf structure although its biological role is obscure (8). Lf, like serotransferrin (Tf), has two iron-binding sites, and iron binding is dependent on bicarbonate (9). Its amino acid sequence is homologous with that of Tf (10, 11) and ovotransferrin (11) and it contains two oligosaccharide chains, which are structurally similar to those of serotransferrin ( Fig. 1), except that additional fucose residues are in a1->3 linkage with the N-acetylglucosamine residues adjacent to galactose and those chains containing fucose are devoid of sialic acid (11, 12, and unpublished observations

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