ABSTRACT
We have identified new malaria vaccine candidates through the combination of bioinformatics prediction of stable protein domains in the Plasmodium falciparum genome, chemical synthesis of polypeptides, in vitro biological functional assays, and association of an antigen-specific antibody response with protection against clinical malaria. Within the predicted open reading frame of P. falciparum hypothetical protein PFF0165c, several segments with low hydrophobic amino acid content, which are likely to be intrinsically unstructured, were identified. The synthetic peptide corresponding to one such segment (P27A) was well recognized by sera and peripheral blood mononuclear cells of adults living in different regions where malaria is endemic. High antibody titers were induced in different strains of mice and in rabbits immunized with the polypeptide formulated with different adjuvants. These antibodies recognized native epitopes in P. falciparum-infected erythrocytes, formed distinct bands in Western blots, and were inhibitory in an in vitro antibody-dependent cellular inhibition parasite-growth assay. The immunological properties of P27A, together with its low polymorphism and association with clinical protection from malaria in humans, warrant its further development as a malaria vaccine candidate.
Subject(s)
Antigens, Protozoan/immunology , Malaria Vaccines/immunology , Plasmodium falciparum/immunology , Protozoan Proteins/immunology , Adult , Amino Acid Sequence , Animals , Antibodies, Protozoan/blood , Antigens, Protozoan/genetics , Humans , Malaria Vaccines/genetics , Mice , Molecular Sequence Data , Plasmodium falciparum/genetics , Polymorphism, Genetic , Protozoan Proteins/genetics , Rabbits , Vaccines, Synthetic/genetics , Vaccines, Synthetic/immunology , Young AdultABSTRACT
The objective of this study was to explore the usefulness of the fractional excretion of magnesium (FEMg2+) in Nigerian chronic renal failure patients (mild to moderate) in determining the severity of renal insufficiency. Plasma and twenty-four hour urine samples were analysed for magnesium and creatinine in thirty-five chronic renal failure patients and twenty-five healthy controls. The mean fractional excretion of magnesium (FEMg2+) was 15.3%(13.6) in the patients and 6.1%(2.3) in the controls and this correlated negatively with the creatinine clearance in both groups (r = -0.343, p < 0.05) in patients and (r = -0.665, p < 0.001) in controls. There was a positive correlation between plasma creatinine and fractional excretion of magnesium in the patients (r = 0.463, p < 0.05) and controls (0.455, p < 0.05). FEMg2+ may therefore be a more sensitive indicator of renal insufficiency and may also be a better indicator of the progression of renal failure.
