Only low antibody levels were obtained from vaccinating human volunteers with single-chain peptide from the Plasmodium falciparum circumsporozoite protein (PfCSP). This resulted in modest protection against sporozoite challenge. In addition, HLA restriction limits the probability of synthesis of a vaccine effective for a diverse population. We report immunization studies with a multiple antigen peptide (MAP) system consisting of multiple copies of a B-cell epitope from the central repeat region of the PfCSP in combination with a universal T-cell epitope, the P2P30 portion of tetanus toxin. This MAP4(NANP)6P2P30 vaccine was highly immunogenic in four different strains of mice when used with various safe and nontoxic adjuvants. When this MAP vaccine was encapsulated in liposomes with lipid A and adsorbed to aluminium hydroxide and given three times at 4-week intervals, the resultant antibody prevented 100% of sporozoites from invading and developing into liver stage infection. This high degree of immunogenicity of MAP4(NANP)6P2P30 vaccine formulated in liposomes, lipid A and aluminum hydroxide provides the foundation for consideration of human trials with this formulation.

Adjuvants, Immunologic↗

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The past and future of laboratory information systems.

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Clinical Laboratory Information Systems↗

PubMedDate not supplied

Low levels of unsaturated transferrin as a predictor of survival in pneumococcal pneumonia.

A study was conducted to evaluate factors which might influence the prognosis of persons with pneumonia owing to Streptococcus pneumoniae. Serum iron, total iron binding capacity and unbound iron binding capacity (UIBC), were evaluated in 35 such patients. Of the 10 patients with UIBC levels less than 130 micrograms per dl on admission to the hospital, six died, three had complications, and only one recovered uneventfully. Of the 25 surviving patients, 21 (84 percent) had UIBC greater than 130 micrograms per dl on admission. Positive blood cultures were also correlated with survival. However, the strongest prognostic indicator was the combination of UIBC and blood culture results. Only 14 percent of patients with abnormalities in both parameters survived, whereas 80 percent to 88 percent of those with negative blood culture and/or normal UIBC survived. This suggests that insufficient unsaturated transferrin may facilitate bacteremia and contribute to lethality of pneumococcal pneumonia.

Humans↗

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Effects of poloxamer 188 in a rabbit model of hemorrhagic shock.

Poloxamer 188 is a synthetic surfactant that reduces the viscosity of whole blood without hemodilution. It is postulated that poloxamer 188 would improve outcome if administered during retransfusion following hemorrhage. Rabbits were anesthetized and instrumented for 3 hours of hemodynamic monitoring. After stabilization, blood was withdrawn over a 5 minute period to reduce mean arterial pressure to 35 mmHg (4.7 kPa). Following a 60 minute shock period, animals were randomly assigned to 1 of 5 experimental groups (n = 8 in each): (1) Shock (no retransfusion); (2) Transfusion (retransfusion of autologous shed blood); (3) Volume (retransfusion with autologous blood and infusion of an additional volume of normal saline equivalent to the volume of poloxamer 188 given in the next 2 experimental groups); (4) Low and (5) High drug (i.v. bolus of 200 mg/kg of poloxamer 188 over 5 minutes at retransfusion, followed by a continuous infusion of poloxamer 188 at 50 mg/kg/hr in the Low drug group and 200 mg/kg/hr in the High drug group). All animals in a surgery Control group (n = 6) remained stable during the 3 hour monitoring period. In contrast, none of the animals in the Shock group remained alive, confirming this to be a relevant model of trauma and severe hemorrhagic shock. There were significantly more animals surviving at the end of the monitoring period in the two groups that received poloxamer 188 (numbers of animals alive after 3 hours = 7 of 8 in the High group and 6 of 8 in the Low group) compared to the Transfusion (4 of 8) and Volume (2 of 8) groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

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Induction of pulmonary granulomas, macrophage procoagulant activity, and tumor necrosis factor-alpha by trehalose glycolipids.

Trehalose 6,6' dimycolate (TDM), a mycobacterial glycolipid, induces granulomas and hemorrhagic toxic reactions when administered in oil but not as a suspension in saline. It was previously demonstrated by us that TDM forms highly structured layers at oil-water interfaces and then postulated that its toxicity derives from the adhesive properties of these layers. To test this hypothesis, an evaluation was made of the ability of TDM and two analogs, trehalose 6-monomycolate (TMM) and galactose-galactose 6, 6' dimycolate (GDM), to induce pulmonary granulomas and stimulate expression of procoagulant activity (PCA) and tumor necrosis factor-alpha (TNF-alpha). Intravenous injection in mice of oil-in-water emulsions of TDM produced more and larger pulmonary granulomas than injection of TMM or GDM. Similarly, TDM on the surface of beads induced higher levels of PCA and TNF-alpha in human mononuclear cells than the analogs. The correlation of these results with the structure of surface layers of the glycolipids strengthens the hypothesis that the particular surface structure formed by TDM is necessary for its biologic activity.

Animals↗

PubMedDate not supplied

Studies on the toxic effects of quartz and a mycobacterial glycolipid, trehalose 6,6'-dimycolate.

Quartz and trehalose 6,6'-dimycolate (TDM) both potentiate tuberculosis and have toxicities that depend on surface crystalline structures. Investigations were undertaken to determine if TDM can kill macrophages and produce hemolysis in a fashion similar to that of quartz and if quartz can induce granulomas similar to those induced by TDM. Trehalose 6,6'-dimycolate was spread as a molecular monolayer on the surface of tissue culture dishes adjacent to areas of uncoated plastic for comparison. Murine peritoneal macrophages were killed within hours by contact with the TDM monolayer, while those on adjacent areas of uncoated plastic remained viable and spread normally. The membranes of erythrocytes were also damaged by contact with the monolayer of TDM. This damage was inhibited by poly-2-vinyl-pyridine-N-oxide, an inhibitor of hydrogen bonding that blocks quartz induced hemolysis. These data suggest that TDM damages membranes via an adhesive mechanism similar to that of quartz. Furthermore, injections of quartz particles into mice induce acute granulomatous reactions similar to those induced by TDM. These data indicate that TDM and quartz have certain similarities in their mechanisms of action and that these similarities may be of importance in the pathogenesis of tuberculosis.

Animals↗