Malaria vaccine: roadblocks and possible solutions

Malaria remains the most prevalent and devastating parasitic disease worldwide. Vaccination is considered to be an approach that will complement other strategies for prevention and control of the disease in the future. In the last 10 years, intense studies aimed at the development of a malaria vaccine have provided important knowledge of the nature of the host immunological mechanisms of protection and their respective target antigens. It became well established that protective immune responses can be generated against the distinct stages of Plasmodium. However, in general, protective immune responses are directed at stage-specific antigens. The elucidation of the primary structure of these antigens made possible the generation of synthetic and recombinant proteins that are being extensively used in experimental immunizations against the infection. Today, several epitopes of limited polymorphism have been described and protective immunity can be generated by immunization with them. These epitopes are being tested as primary candidates for a subunit vaccine against malaria. Here we critically review the major roadblocks for the development of a malaria vaccine and provide some insight on how these problems are being solved

The use of protein structure/activity relationships in the rational design of stable particulate delivery systems

The recombinant heat shock protein (18 kDa-hsp) from Mycobacterium leprae was studied as a T-epitope model for vaccine development. We present a structural analysis of the stability of recombinant 18 kDa-hsp during different processing steps. Circular dichroism and ELISA were used to monitor protein structure after thermal stress, lyophilization and chemical modification. We observed that the 18 kDa-hsp is extremely resistant to a wide range of temperatures (60% of activity is retained at 80ºC for 20 min). N-Acylation increased its ordered structure by 4% and decreased its ß-T1 structure by 2%. ELISA demonstrated that the native conformation of the 18 kDa-hsp was preserved after hydrophobic modification by acylation. The recombinant 18 kDa-hsp resists to a wide range of temperatures and chemical modifications without loss of its main characteristic, which is to be a source of T epitopes. This resistance is probably directly related to its lack of organization at the level of tertiary and secondary structures.

Mathematical modeling of electro-rotation spectra of small particles in liquid solutions: Application to human erythrocyte aggregates

Electro-rotation can be used to determine the dielectric properties of cells, as well as to observe dynamic changes in both dielectric and morphological properties. Suspended biological cells and particles respond to alternating-field polarization by moving, deforming or rotating. While in linearly polarized alternating fields the particles are oriented along their axis of highest polarizability, in circularly polarized fields the axis of lowest polarizability aligns perpendicular to the plane of field rotation. Ellipsoidal models for cells are frequently applied, which include, beside sphere-shaped cells, also the limiting cases of rods and disks. Human erythrocyte cells, due to their particular shape, hardly resemble an ellipsoid. The additional effect of rouleaux formation with different numbers of aggregations suggests a model of circular cylinders of variable length. In the present study, the induced dipole moment of short cylinders was calculated and applied to rouleaux of human erythrocytes, which move freely in a suspending conductive medium under the effect of a rotating external field. Electro-rotation torque spectra are calculated for such aggregations of different length. Both the maximum rotation speeds and the peak frequencies of the torque are found to depend clearly on the size of the rouleaux. While the rotation speed grows with rouleaux length, the field frequency nup is lowest for the largest cell aggregations where the torque shows a maximum.

Osmotic dehydration of sweet potato (Ipomoea batatas) in ternary solutions

The aim of this work was to evaluate the osmotic dehydration of sweet potato (Ipomoea batatas) using hypertonic sucrose solutions, with or without NaCl, at three different concentrations, at 40 °C. Highest water losses were obtained when the mixture of sucrose and NaCl was used. The addition of NaCl to osmotic solutions increases the driving force of the process and it is verified that the osmotic dehydration process is mainly influenced by changes in NaCl concentration, but the positive effect of the salt-sucrose interaction on soluble solids also determined the decrease of solid gain when solutes were at maximum concentrations. Mass transfer kinetics were modeled according to Peleg, Fick and Page's equations, which presented good fittings of the experimental data. Peleg's equation and Page's model presented the best fitting and showed excellent predictive capacity for water loss and salt gain data. The effective diffusivity determined using Fick's Second Law applied to slice geometry was found to be in the range from 3.82 x 10-11 to 7.46 x 10-11 m²/s for water loss and from 1.18 x 10-10 to 3.38 x 10-11 m²/s for solid gain.

Effect of standard and neutral-pH peritoneal dialysis solutions upon fibroblasts proliferation

Introduction: Continuous exposition of the peritoneal membrane to conventional dialysis solutions is an important risk factor for inducing structural and functional alterations. Objective: To compare in vitro mouse fibroblast NIH-3T3 cell viability after exposition to a neutral pH dialysis solution in comparison to cells exposed to a standard solution. Methods: Experimental study to compare the effects of a conventional standard or a neutral-pH, low-glucose degradation products peritoneal dialysis solution on the viability of exposed fibroblasts in cell culture. Both solutions were tested in all the commercially available glucose concentrations. Cell viability was evaluated with tetrazolium salt colorimetric assay. Results: Fibroblast viability was significantly superior in the neutral pH solution in comparison to control, in all three glucose concentrations (Optical density in nm-means ± SD: 1.5% 0.295 ± 0.047 vs. 0.372 ± 0.042, p < 0.001; 2.3% 0.270 ± 0.036 vs. 0.337 ± 0.051, p < 0.001; 4.25% 0.284 ± 0.037 vs. 0.332 ± 0.032, p < 0.001; control vs. neutral pH respectively, Student t Test). There was no significant difference in cell viability between the three concentrations of glucose when standard solution was used (ANOVA p = 0.218), although cell viability was higher after exposition to neutral pH peritoneal dialysis fluid at 1.5% in comparison to 2.3 and 4.25% glucose concentrations (ANOVA p = 0.008: Bonferroni 1.5% vs. 2.3% p = 0.033, 1.5% vs. 4.25% p = 0.014, 2.3% vs. 4.25% p = 1.00). Conclusion: Cell viability was better in neutral pH dialysis solution, especially in the lower glucose concentration. A more physiological pH and lower glucose degradation products may be responsible for such results.

Democracia e eficiência: a difícil relação entre política e economia no debate contemporâneo

Democracy and efficiency: hard relations between politics and economy. Many economists see politics as an irrational activity. They also think state action usually generates market inefficiencies and democratic institutions, such as elections, often work as obstacles to sound economic measures. Showing that vision has been embedded into the main currents of economic thought since the last century, we also argue those ideas are exported to great part of contemporary political science, including the area of public policies. Examining the literature, we show that rational choice political scientists, as the economists, claim governability and effective decisions will be guaranteed mainly through concentrated arenas or through insulated arrangements able to protect policy makers from political interference. In other words, governability depends on the reduction of the political arenas. On the contrary, we reject this technocratic solution of splitting politics from economy. With the support of classical pluralist thinkers, we stand another conception, arguing politics is the privileged social space for building interests and values in an institutionalized way. The difficulties to surpass current international crises since 2008 reveal this is a crucial problem: reducing politics would prevent societies from improving institutional solutions which are the only ones able to give space to emerging conflicts and, then, reach eventual consensus around them.

Has social justice any legitimacy in Kant's theory of right? The empirical conditions of the legal state as a civil union

This paper aims at shedding light on an obscure point in Kant's theory of the state. It discusses whether Kant's rational theory of the state recognises the fact that certain exceptional social situations, such as the extreme poverty of some parts of the population, could request institutional state support in order to guarantee the attainment of a minimum threshold of civil independence. It has three aims: 1) to show that Kant's Doctrine of Right can offer solutions for the complex relation between economics and politics in our present time; 2) to demonstrate the claim that Kant embraces a pragmatic standpoint when he tackles the social concerns of the state, and so to refute the idea that he argues for an abstract conception of politics; and 3) to suggest that a non-paternalistic theory of rights is not necessarily incompatible with the basic tenets of a welfare state.