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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A synthetic gene encoding a tetramer of the repeated subunit EENVEHDA of the Plasmodium falciparum antigen Pf155/RESA was expressed in a dual-expression system. The resulting fusion proteins, designated ZZ-M1 and BB-M1, comprised the EENVEHDA repeats and either two immunoglobulin G-binding domains from staphylococcal protein A or the human serum albumin-binding domains from streptococcal protein G, respectively. The soluble fusion proteins were affinity purified to homogeneity in one-step procedures. ZZ-M1 was used for immunization of rabbits. The rabbit antisera reacted with BB-M1 in an enzyme-linked immunosorbent assay and with Pf155/RESA in immunofluorescence of infected erythrocytes and immunoblotting. Inhibition studies revealed that the antibodies mainly recognized epitopes formed by two or more EENVEHDA subunits and were remarkably specific for Pf155/RESA. Importantly, the antibodies also inhibited P. falciparum merozoite reinvasion in vitro efficiently, indicating that they reacted with biologically important epitopes exposed on the native antigen. Immunization with Freund complete adjuvant resulted in high levels of specific immunoglobulin G antibodies over a 1-year period, whereas the antibody response obtained after immunization without adjuvant was generally weaker, immunoglobulin G and M mediated, and not sustained for longer periods. However, these titers were restored after booster injection. Taken together, the results support the usefulness of recombinant gene constructs of this type as immunogens for malaria vaccines.
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PMID:Immunogenicity and antigenicity in rabbits of a repeated sequence of Plasmodium falciparum antigen Pf155/RESA fused to two immunoglobulin G-binding domains of staphylococcal protein A. 218 Aug 22

The Plasmodium falciparum-derived antigen of Mr 155,000 designated Pf 155, deposited in the membrane of infected erythrocytes, contains at least two blocks of tandemly repeated amino acid sequences. The peptide Glu-Glu-Asn-Val-Glu-His-Asp-Ala, which corresponds to a subunit of a C-terminally located repeat, was synthesized. Rabbits immunized with the octapeptide conjugated with either keyhole limpet hemocyanine or tetanus toxoid formed antibodies against the octapeptide. These antibodies reacted with Pf 155 as detected by immunoblotting or a modified immunofluorescence assay. Sera from humans exposed to P. falciparum also contained antibodies binding to the octapeptide in a dot-blot immunoassay. Their anti-octapeptide titers were correlated with their immunofluorescence titers in the assay detecting Pf 155 and other parasite antigens in the membrane of infected erythrocytes. Human octapeptide-reactive antibodies were isolated on an affinity column with the octapeptide conjugated to bovine serum albumin as ligand. These human antibodies reacted with Pf 155 in immunoblotting and strongly stained the surface of infected erythrocytes in the modified immunofluorescence assay. Approximately 20% of this immunofluorescence activity in a high-titered human serum could be recovered from the octapeptide column, indicating that a significant fraction of these anti-parasite antibodies react with epitopes associated with the octapeptide. Furthermore, the human octapeptide-reactive antibodies very efficiently inhibited merozoite reinvasion into erythrocytes in vitro. Similarly purified rabbit antibodies also significantly inhibited reinvasion. Our results suggest that the C-terminal segment of repeated peptides in Pf 155 is a major antigenic region of the molecule and may contain target sites for protective immunity in P. falciparum malaria.
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PMID:Rabbit and human antibodies to a repeated amino acid sequence of a Plasmodium falciparum antigen, Pf 155, react with the native protein and inhibit merozoite invasion. 241 97

The majority of malaria antigens that have been cloned contain short sequence repeats which encode antigenic epitopes that are naturally immunogenic. Synthetic peptides have been used to show that natural antibody responses to a strain-specific Plasmodium falciparum S antigen are largely directed against epitopes encoded in an 11-amino acid sequence that is repeated approximately 100 times in the molecule. A 16-amino acid peptide conjugated to bovine serum albumin induced antibodies specific for the S antigen of the homologous isolate. Synthetic peptides have also been used to confirm the natural immunogenicity of epitopes encoded within two blocks of related repeats in the Ring-infected Erythrocyte Surface Antigen (RESA). A 16-amino acid peptide, comprising four repeats of the tetrameric sequence EENV, induced antibodies reactive with the native molecule. Detailed analyses of these anti-peptide antisera indicate that short sequence repeats express more than one epitope, some of which may cross-react with other repeat structures.
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PMID:Antigenic repeat structures in proteins of Plasmodium falciparum. 242 51

We tested the hypothesis that cerebral malaria is caused by blood-brain barrier inflammation and cerebral edema. In a group of 157 Thai patients with strictly defined cerebral malaria, cerebrospinal fluid (CSF) opening pressures were normal in 79% and were lower in fatal cases than in survivors (means +/- 1 SD, 144 +/- 58 and 167 +/- 51 mm CSF, respectively, P = 0.051). CSF: serum albumin ratios (X 10(3)) in 39 of them were significantly higher than in 61 British controls (medians 8.5 and 5.5, respectively, P = 0.04), but were no higher in 7 fatal cases. In a group of 12 patients this ratio was not significantly higher during coma than after full recovery (means +/- 1 SD, 9.0 +/- 6.2 and 6.7 +/- 4.2, respectively, P greater than 0.1). CSF alpha 2-macroglobulin concentrations were always normal. CSF : serum 77Br- ratios were elevated in 11/19 comatose cases but fell to normal 4 to 9 days later in 11/11 cases. Dexamethasone treatment had no significant effect on bromide partition. The percentage of an intravenously administered dose of 125I-human serum albumin detectable per ml of CSF 6 hr after intravenous injection was 2.4 +/- 1.3 X 10(-5) in 14 comatose patients and 4.4 +/- 4.0 X 10(-5) in 9 of them during convalescence (P greater than 0.1). These results demonstrate that the blood-CSF barrier is essentially intact in patients with cerebral malaria and give no support to the idea that cerebral edema is the cause of coma.
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PMID:Function of the blood-cerebrospinal fluid barrier in human cerebral malaria: rejection of the permeability hypothesis. 242 67

A/J and CBA/H mice infected with Plasmodium berghei ANKA, a murine model of cerebral malaria, were used to see whether antioxidants influenced the outcome of this disease. Untreated, infected mice died 7 to 9 days after infection, often with cerebral symptoms. Haemorrhages, mononuclear infiltration and oedema were present in the central nervous system (CNS). Feeding a diet containing 0.75% (w/w) butylated hydroxyanisole (BHA) greatly altered the course of this disease. Death was delayed by up to 2 weeks and mice appeared healthy at parasitaemias that would have caused cerebral symptoms and death had they been on a conventional diet. BHA-fed mice showed few or no cerebral symptoms at a time at which control mice were clearly affected, and greatly reduced haemorrhages, mononuclear infiltration and oedema when the CNS was examined. Similar, but more consistent, protective effects were seen after administration of BHA by repeated injections or in osmotic pumps. The combination of superoxide dismutase and catalase, coupled to polyethylene glycol, when administered intravenously also protected mice against death from cerebral complications. Permeability of the blood-brain barrier was monitored by the use of 125I-labelled bovine serum albumin, 51Cr-labelled erythrocytes and the dye Evans blue, all of which are normally excluded from the CNS. Infected mice on control diet showed an increase in Evans blue staining and 125I and 51Cr retention in the CNS tissue itself. Feeding the diet containing BHA reduced these indices of increased blood-brain barrier permeability. In view of the potent radical scavenging activity of BHA in many other systems it is likely, but unproven, that this is its main role here. The protective effect of superoxide dismutase and catalase lends support to the idea that reactive oxygen species are involved in the pathology of experimental cerebral malaria.
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PMID:Antioxidants can prevent cerebral malaria in Plasmodium berghei-infected mice. 266 24

A novel dual expression system for the generation and analysis of immune responses to recombinant protein is described. The two expression systems are based on the IgG-binding domains (ZZ) of staphylococcal protein A (SpA) and the human serum albumin (HSA) binding domains (BB) of streptococcal protein G, respectively. Products of fusions with the ZZ region are used to generate an immune response against the recombinant peptide and the corresponding peptide fused to the BB region is used for analysis and purification of the specific antibodies. The protein A and protein G expression systems were used to produce fusion proteins with the repeated C terminal octapeptide subunit EENVEHDA of the Plasmodium falciparum merozoite derived protein Pf155/RESA. Rabbits were immunized with the protein A-derived fusion protein (designated ZZ-M1) and the antibody response was analyzed using the protein G-derived fusion protein (designated BB-M1). The rabbit antisera reacted with BB-M1 in both ELISA and immunoblotting. In addition, BB-M1 proved to be an efficient ligand for affinity purification of antibodies specific for the malaria peptide. Furthermore, the rabbit antisera reacted with Pf155/RESA both in merozoite extracts and when deposited in the membrane of parasite infected erythrocytes.
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PMID:A dual expression system for the generation, analysis and purification of antibodies to a repeated sequence of the Plasmodium falciparum antigen Pf155/RESA. 268 27

An enzyme-linked immunosorbent assay for rapid detection of malarial antibodies and antigens was developed. Plasmodium falciparum antigen preparation, obtained from sonicated cultures of the parasite at a parasitemia of 10%-15%, was applied to cellulose filter discs in volumes of 0.1 microliter in 96-well microtiter plates. Antibodies were detected by successive incubations with: bovine serum albumin for blocking, tested serum at different dilutions, peroxidase-conjugated antihuman IgG, and the precipitable substrate 4-chloro-1-naphtol. Positive reactions appeared as blue dots on a white background which are easily read by eye. Pools of sera from patients with recent disease or from individuals with a history of malaria, contained antibodies detectable up to a dilution of 1:64,000. Negative results were obtained when normal RBC were used for dotting the filters. Normal sera showed no reaction at any antigen concentration. P. falciparum antigens were detected by their ability to inhibit the binding of antibody to the filters. RBC infected with P. falciparum in vitro can be detected at a level of 0.001% parasitemia. This report presents the feasibility of an assay for detecting malarial antibodies and antigens in blood samples which is easily applicable to field conditions.
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PMID:The feasibility of a Dot enzyme-linked immunosorbent assay (Dot-ELISA) for the diagnosis of Plasmodium falciparum antigens and antibodies. 354 51

The immune response of young Nigerian children to a full course of infant immunizations was studied in relation to their nutritional state at the time of vaccination. No significant correlations were found between anthropometric measurements made at the time of vaccination and the antibody response to triple, polio, measles, meningococcal and typhoid vaccines. Significant correlations were found between serum pre-albumin levels and the response to group A meningococcal polysaccharide vaccine and between serum albumin levels and the response to group C meningococcal polysaccharide vaccine. These correlations may reflect the depressive effect of malaria both on serum albumin and pre-albumin levels and on immune responsiveness to meningococcal polysaccharides. No significant correlations were found between nutritional state at the time of BCG vaccination and the development of a positive tuberculin reaction five weeks later. We conclude that under-nutrition has little or no effect on the immune response to vaccines used in routine infant immunization programmes.
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PMID:The immune response to vaccination in undernourished and well-nourished Nigerian children. 363 2

The nutrition of a group of Nigerian children who received weekly chemoprophylaxis with chloroquine during their first one or two years of life was compared with the nutrition of a group of children exposed frequently to malaria. Fewer episodes of severe malnutrition and fewer deaths from malnutrition occurred among protected than among control children. Protected children tended to be taller and heavier than control children and to have a larger mid-upper arm circumference. Mean serum albumin and pre-albumin levels were higher in protected than in control children. However differences between the two groups were small and only in a few instances were they statistically significant.
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PMID:Malaria chemoprophylaxis with chloroquine in young Nigerian children. III. Its effect on nutrition. 393 35

Suppression of antibody producing splenic lymphocytes by plasma from rats infected with Plasmodium chabaudi malaria was confirmed. Suppressive activity was found in plasma drawn on the sixth, seventh and eighth day of infection. It was temporally associated with anemia, elevated levels of soluble immune complex, reduced titers of lytic complement and elevated titers of immunoconglutinin (IK) in the plasma. Heat inactivation of the plasma to destroy complement and removal of IK by absorption did not reduce the suppressive activity. Incubating the plasma-treated lymphocytes with normal rat complement largely, but not completely, reversed the suppressive action. Soluble immune complexes prepared from bovine serum albumin (BSA) and antiBSA (BSA-antiBSA) alexinated complex (BSA-antiBSA-C') and immunoconglutinated complex (BSA-antiBSA-C'-IK) each suppressed the capacity of splenic lymphocytes from rats immunized with sheep blood cells to produce hemolytic Jerne plaques. Incubating the complex-treated cells with fresh complement largely reversed the suppressive activity. It is suggested that the suppressed responses of lymphocytes from malarious animals to antigens or mitogens, reported by others, may have been in part induced by complexes in blood of the animals, and that antibody producing cells might also have been suppressed. Since suppressive activity was not influenced by complement inactivation, but was reversed when plasma-treated cells were incubated with fresh complement, it is suggested that the hypocomplementemic state of suppressive plasma may have contributed to immunosuppression.
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PMID:Reversal of immunosuppression induced with plasma of malarious rats by supplemented complement. 398 48


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