Preparation and preclinical evaluation of a novel liposomal complete-core lipopolysaccharide vaccine.

Our objective is to develop a prophylactic vaccine strategy that can be evaluated for surgical and other high-risk hospitalized patients. In this paper, we describe the preparation and preclinical evaluation of a liposomal complete-core lipopolysaccharide (LPS) vaccine that is nontoxic and broadly antigenic. Complete-core (Ra-chemotype) LPSs were isolated from four gram-negative bacterial strains (Escherichia coli K-12, E. coli R1, Pseudomonas aeruginosa PAC608, and Bacteroides fragilis), mixed together to form a cocktail of complete-core LPSs, and then incorporated into multilamellar liposomes consisting of dimyristoyl phosphatidyl choline, dimyristoyl phosphatidylglycerol, and cholesterol in a 4:1:4 molar ratio. The endotoxic activities of these LPS-containing liposomes were less than 0.1% of the endotoxicities of the original free LPSs as measured by the Limulus amoebocyte lysate assay. In vivo administration of liposomal complete-core LPS mixed with Al(OH)(3) to rabbits resulted in no pyrogenicity or overt toxicity over a 7-day period. In immunoblots, sera from rabbits following active immunization elicited cross-reactive antibodies to a large panel of rough and smooth LPSs from numerous clinically relevant gram-negative bacteria, including E. coli (serotypes O1, O4, O6, O8, O12, O15, O18, O75, O86, O157, and O111), P. aeruginosa (Fisher-Devlin serotypes 1, 2, and 3, which correspond to International Antigenic Typing Scheme types 6, 11, and 2, respectively), Klebsiella pneumoniae (serotypes O1, O2ab, and O3), B. fragilis, and Bacteroides vulgatus. Active immunization of mice with liposomal complete-core LPS provided protection against a lethal challenge with E. coli O18 LPS. The vaccine tested was nontoxic, nonpyrogenic, and immunogenic against a wide variety of pathogens found in clinical settings.

Metals of the bottom muds in Belize City Harbor, Belize.

Seven bottom samples extending from the ocean up through Belize Harbor and City were acid leached (EPA method 200.7) and analyzed using inductively coupled plasma spectrometry to measure the bioavailability of Cd, Cr, Cu, Pb and Zn. Soil and environmental chemists would compare data to world averages of unpolluted soils, these samples were higher than this average by a factor of 10 for Cd, 4 for Cu, 2.7 for Zn and 2.6 for Pb. Geochemists argue that it's hard to find unpolluted soil so their comparison is with world average of ancient (pre-man) shales and the Belize samples were higher than this shale average by a factor of 30 for Cd, 3.7 for Pb, 2.2 for Cu and 1.7 for Zn. Ecologists would argue that the metal effect on the biota is the correct way to analyze the data by using the biological effects toxicity method, and this way the samples were above the lower limit by a factor of 5.1 for Cd, 2.9 for Cu and 1.6 for Pb. By all three lines of reasoning, it can be concluded that Cd, Cu, Pb and Zn, in that order, pose environmental problems. Since this site is located in the middle of Belize Barrier Reef, a highly sensitive environmental area that is also economically important to Belize, it poses a critical problem that needs to be addressed further.

Metals of the bottom muds in Townsville Harbor, Australia.

Samples of Townsville Harbor bottom mud were acid leached (0.3 m HCl) to measure bioavailability of Cd, Co, Cu, Fe, Mn, Ni, Pb, Sn and Zn. Three of seven samples showed enrichment factors relative to average soil of 25-30 for Cd, 5-71 for Cu, 21-81 for Pb, and 13-37 for Zn. The other four samples were only high in Cd, Pb, and Zn by an enrichment factor of 2-7. Considering that this harbor is in the middle of the environmentally sensitive Great Barrier Reef area, the disposal of the dredged harbor muds poses a special problem.

Mechanisms of trace metal transport in rivers.

Trace metals transported by the Amazon (and Yukon rivers were analytically partitioned among the transport phases: in solutions, ion exchange, organic materials, metallic coatings, and crystalline solids. The distribution for both rivers is similarly proportioned, with copper and chromium transported mainly in the crystalline solids, manganese in coatings, and iron, nickel, and cobalt distributed equally between precipitated metallic coatings and crystalline solids.

Mechanisms controlling world water chemistry.

On the basis of analytical chemical data for numerous rain, river, lake, and ocean samples, the three major mechanisms controlling world surface water chemistry can be defined as atmospheric precipitation, rock dominance, and the evaporation-crystallization process.

Amazon river: environmental factors that control its dissolved and suspended load.

Analytical results of sampling during both wet and dry seasons along the Amazon River, at its mouth, and from 16 tributaries reveal that the physical weathering dominant in the Andean mountainous environment controls both the overall composition of the suspended solids discharged by the Amazon and the amount of dissolved salts and suspended solids discharged.