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responses of t cells from sensitized donors to recombinant and synthetic peptides corresponding to sequences of the plasmodium falciparum serp antigen.in the present work, we intend to determine the capacity of human lymphocytes to recognize subfragments of the serine-stretch protein serp, a blood-stage antigen from plasmodium falciparum. individuals sensitized by a previous p. falciparum infection were studied. some recombinant proteins (rp) including rp7 and rp10 (amino acids 631-684 and 631-892 of serp, respectively), were recognized in proliferation assays by lymphocytes from 28 sensitized individuals and not by lymphocytes from control, n ...19901704344
amino acid sequences recognized by t cells: studies on a merozoite surface antigen from the fcq-27/png isolate of plasmodium falciparum.twenty-six overlapping peptides, spanning the entire fcq-27/png sequence of the plasmodium falciparum antigen known as merozoite surface antigen 2 were screened for their ability to induce the proliferation of peripheral blood lymphocytes (pbl) obtained from 12 donors living in honiara, solomon islands where p. falciparum is endemic. a recombinant (r) form of msa2, known as ag 1609 was also screened in these assays and tetanus toxoid (tt) antigen was included as a control. the location of the pr ...19901704345
variation of t cell epitopes of the plasmodium falciparum cs protein: its occurrence, extent and relevance. 19901704346
longitudinal study of the cellular response to pf155/resa and circumsporozoite protein in madagascar.in a community follow-up conducted in the central highlands of madagascar, the cellular responses to synthetic peptides from the immunodominant regions of pf155/resa and the repeat region of the circumsporozoite protein were studied. seasonal variations of the t cell response were measured at the individual level; the relationship between this response and the presence of parasites in blood was assessed; the question of the possible protective value of the lymphocyte proliferation in presence of ...19901704347
isolation and characterization of protective cytolytic t cells in a rodent malaria model system.protective immunity against malaria is induced by immunization with irradiation-attenuated sporozoites. here we report the isolation of cytolytic t-cell (ctl) clones from balb/c (h-2d) mice immunized with either plasmodium berghei or plasmodium yoelii sporozoites. the epitopes recognized by these ctl can be mimicked by synthetic peptides corresponding to a homologous region in the cs proteins of both rodent malaria species. both peptides are recognized by the ctl in the context of the same mhc c ...19901704348
protective anti-sporozoite antibodies induced by a chemically defined synthetic vaccine.chemically defined synthetic polymers, known as multiple antigen peptide systems (maps) represent an effective and novel approach for engineering peptide-based vaccines. ten different mono and diepitope map models, containing different arrangements and stoichiometry of functional b and/or t helper epitopes from the circumsporozoite protein of plasmodium berghei were used to immunize mice. high titers of antibody and protective immunity against sporozoite challenge were elicited by maps containin ...19901704349
peptide-primed cd4+ cells and malaria sporozoites.we have mapped a t cell epitope in the circumsporozoite (cs) protein of the murine malaria parasite, plasmodium yoelii. a 21-mer synthetic peptide corresponding to the amino acid positions 59-79 (referred to as py1), induced specific proliferation in balb/c and c57bl/6 mice, and provided help for the production of antibodies to peptides from the repetitive region, (qgpgap)n, of the same cs protein, when mice were immunized with the py1 peptide conjugated to the repetitive peptide. long-term cd3+ ...19901704350
plasmodium falciparum sexual stage antigens: immunogenicity and cell-mediated responses.antibody and cell-mediated immune responses to the transmission-blocking target antigens of plasmodium falciparum, pfs 48/45, were determined in infected non-immune patients and in immune individuals from an endemic area. characterization of the b cell epitopes with monoclonal antibodies showed that there were five regions identifiable but there could be interactions between them causing either competitive or enhancing effects. sera from infected non-immune patients contained antibodies that wou ...19901704351
immunogenicity of plasmodium falciparum sexual stage antigens: implications for the design of a transmission blocking vaccine.immunogenicity of sexual stage antigens and boosting of transmission blocking antibodies following a natural infection are two critical factors in the design of an effective, subunit vaccine to block the transmission of malaria from man to mosquito. immunogenicity and boosting are both t cell-dependent. antigens, such as the 230-kda, the 48/45-kda, and the 40/10-kda, expressed early in the extracellular forms of the sexual stage of plasmodium falciparum, have limited immunogenicity in humans and ...19901704352
t cell epitopes of the circumsporozoite protein of plasmodium vivax. recognition by lymphocytes of a sporozoite-immunized chimpanzee.the humoral and cellular antisporozoite immune responses of a laboratory-born chimpanzee were measured following multiple exposures to the bites of plasmodium vivax-infected mosquitoes. t cell lines and clones derived from the chimpanzee's pbl were used to identify t cell epitopes of the p. vivax circumsporozoite (cs) protein. two independently obtained cell lines, established by culturing the pbl with either a recombinant p. vivax circumsporozoite (rpvcs) protein or a pool of synthetic peptides ...19911704402
opsonization as an effector mechanism in human protection against asexual blood stages of plasmodium falciparum: functional role of igg subclasses.a phagocytic assay performed with human peripheral mononuclear cells and malaria-infected erythrocytes enabled the study of opsonizing antibodies in human serum from donors presenting different levels of protective immunity. opsonizing activity was found in sera from individuals who could be considered immune, i.e. asymptomatic parasite carriers and subjects residing in endemic regions who presented neither symptoms nor parasites. this contrasted with subjects showing an absence of symptoms or w ...19901704637
the antibody response in balb/c mice to the plasmodium falciparum circumsporozoite repetitive epitope covalently coupled to synthetic lipopeptide adjuvant.the repetitive epitope of plasmodium falciparum circumsporozoite protein (asn-ala-asn-pro)3 [(nanp)3] was coupled to tripalmitoyl-s-glyceryl-cysteine (p3c) and tripalmitoyl-s-glyceryl-cysteinyl-serine (p3cs). the lipopeptide p3cs is a potent b-cell and macrophage activator. the resulting immunogenic lipopeptides were used for immunization of the low responder mouse strain balb/c. these low molecular weight conjugates induced specific anti-(nanp)3 igg and igm levels without any carrier proteins o ...19911705236
rapid diagnosis of malaria by fluorescence microscopy. 19911705646
characterization of a plasmodium falciparum epitope recognized by a monoclonal antibody with broad isolate and species specificity.monoclonal antibody (mab) 7h8 raised against plasmodium yoelii reacted with a series of proteins from p. falciparum that range in molecular weight from 46 to 194 kda. by immunofluorescence assay, this mab reacted with all isolates of p. falciparum tested. mab 7h8 was used to screen a genomic expression library of asexual blood stage antigens of p. falciparum, malayan camp k+ and 7 independent clones were identified. these 7 clones were sequenced and the epitope recognized by mab 7h8 in the recom ...19901706114
growth inhibition of plasmodium falciparum in in vitro cultures by selective action of tryptophan-n-formylated gramicidin incorporated in lipid vesicles.we studied the differential effect of tryptophan-n-formylated gramicidin on uninfected and plasmodium falciparum-infected erythrocytes. trp-n-formylated gramicidin induces a much faster leakage of k+ from infected cells than from uninfected cell whereas, and at an even lower concentration, gramicidin a' causes a rapid k+ leakage from both uninfected and infected cells. we also studied the effect of trp-n-formylated gramicidin and gramicidin a' incorporated in liposomes on the growth of plasmodiu ...19911706202
circumsporozoite protein genes of malaria parasites (plasmodium spp.): evidence for positive selection on immunogenic regions.the circumsporozoite (cs) protein is a cell surface protein of the sporozoite, the stage of the life cycle of malaria parasites (plasmodium spp.) that infects the vertebrate host. analysis of dna sequences supports the hypothesis that in plasmodium falciparum, positive darwinian selection favors diversity in the t-cell epitopes (peptides presented to t cells by host mhc molecules) of the cs protein. in gene regions encoding t cell epitopes of p. falciparum, the rate of nonsynonymous nucleotide s ...19911706291
major population differences in t cell response to a malaria sporozoite vaccine candidate.using a complete series of overlapping peptides, we have identified the t cell epitopes of a malaria vaccine candidate, the circumsporozoite (cs) protein, that are recognized by sporozoite-exposed residents of a non-endemic country. this protein and subunits from it are being considered as malaria sporozoite vaccine candidates, as cs-specific antibodies and cytotoxic t lymphocytes have been shown to have a role in protection. the rationale for developing an antibody-based vaccine is that in plas ...19901706620
review: cytokines and malaria.malaria, which is caused by hemoprotozoan parasites of the genus plasmodium, has once again reached epidemic proportions. the resurgence of malaria has occurred because the parasite has developed resistance to the anti-malarial drugs and the mosquito vector has developed resistance to the insecticides. added to these impediments is the problem that, in spite of intense efforts by researchers world-wide, there is yet no effective anti-malarial vaccine. our lack of knowledge concerning the exact m ...19901706648
measurement of acute phase proteins for assessing severity of plasmodium falciparum malaria.seventeen adult patients with acute plasmodium falciparum malaria, admitted to the hospital for tropical diseases, were studied. serial measurements of the serum concentration of c-reactive protein, serum amyloid a protein, and percentage parasitaemia were determined, together with initial measurement of serum electrolytes, liver function, haemoglobin, white cell and platelet counts. initial c-reactive protein and serum amyloid a concentrations were increased (c-reactive protein mean 49.0 mg/l s ...19911707416
properties of epitopes of pfs 48/45, a target of transmission blocking monoclonal antibodies, on gametes of different isolates of plasmodium falciparum.we have studied the properties of epitopes on plasmodium falciparum gamete surface protein pfs 48/45, a target antigen of malaria transmission blocking antibodies. using a two site immunoradiometric assay we have defined three spacially separate, non-repeated, epitope regions on the peptides representing this antigen. epitope region i is a target of monoclonal antibodies (moabs) which strongly suppress infectivity of gametocytes of p. falciparum to mosquitoes; the effect is complement independen ...19901707506
clonal repertoire analysis of murine b cells specific for repeat sequence antigens of plasmodium falciparum.clonal analysis of the murine b-cell repertoire has been used to investigate the possible role of tandem repeat sequence epitopes of plasmodium falciparum in immune evasion. a limiting dilution culture system was used whereby murine spleen cells were stimulated with the b-cell mitogen lipopolysaccharide (lps) in the presence of 3t3 fibroblast filler cells. one in three b cells were shown to produce clones secreting immunoglobulin measurable by an elisa. the frequency of antibody forming cell pre ...19901707507
many peptide fragments of alien antigens are homologous with host proteins, thus canalizing t-cell responses.all proteins of this world are constructed in compliance with the same rule. accordingly, two totally unrelated proteins, on the average, share 30 identical tripeptides, two tetrapeptides, and one pentapeptide per 500 residues. with this in mind, the 221-residue-long influenza virus hemagglutinin ii (ivha-ii), as a representative of alien antigens, was compared with three diverse proteins representing the host: 533-residue-long chicken c-src protein kinase (c-src product of the cellular oncogene ...19911707530
sequestrin, a cd36 recognition protein on plasmodium falciparum malaria-infected erythrocytes identified by anti-idiotype antibodies.the cd36 molecule expressed by human endothelial cells is a receptor for the adhesion of erythrocytes infected with the human malaria parasite plasmodium falciparum. a cd36-specific monoclonal antibody, okm8, inhibits the adhesion of malaria-infected erythrocytes (irbc) to purified cd36 and cells expressing cd36. monospecific polyclonal anti-idiotype (anti-id) antibodies, raised against monoclonal antibody okm8, expressed determinants molecularly mimicking the cd36 binding domain for the adhesio ...19911707534
human cytotoxic t lymphocytes against the plasmodium falciparum circumsporozoite protein.cytotoxic t lymphocytes (ctl) against the circumsporozoite (cs) protein of malaria sporozoites protect against malaria in rodents. although there is interest in developing human vaccines that induce ctl against the plasmodium falciparum cs protein, humans have never been shown to produce ctl against any plasmodium species protein or other parasite protein. we report that when peripheral blood mononuclear cells (pbmc) from three of four volunteers immunized with irradiated p. falciparum sporozoit ...19911707538
identification of epitopes within the circumsporozoite protein of plasmodium vivax recognized by murine t lymphocytes.the murine cellular immune response to the circumsporozoite (cs) protein of plasmodium vivax was characterized using five synthetic peptides, some of which we identified as corresponding to t cell epitopes. the peptides p308-320, p344-355 and p353-364 were immunogenic, inducing a genetically restricted proliferative response, due to the activation of cd4+ t cells. the peptide p308-320 was recognized only by the lymphocytes of b10 (h-2b) mice. the other two peptides were recognized by primed lymp ...19911707825
demonstration of alternative splicing of a pre-mrna expressed in the blood stage form of plasmodium falciparum.by screening of a lambda gt11 library from plasmodium falciparum genomic dna with an antiserum raised against a 41-kda protein band, which was shown to confer protective immunity to monkeys, the phage clone 41-3 was identified. the entire 41-3 gene was isolated, and its coding regions were determined by amplification and sequencing of 41-3 specific mrna fragments. the 41-3 gene has a complex structure consisting of nine exons, encoding 375 amino acids in total with a calculated molecular weight ...19911707880
mechanisms of t cell recognition with application to vaccine design.both helper and cytotoxic t lymphocytes generally recognize protein antigens not in their intact form, as antibodies do, but on the surface of another cell, after "processing" by that cell to unfold or cleave the protein into fragments and after association of the processed antigen with major histocompatibility complex (mhc) molecules on that cell. this complex process leads to immunodominance of certain segments from the protein, which depends not only on structural features intrinsic to the an ...19911708102
activities of pefloxacin and ciprofloxacin against experimental malaria in mice.we investigated the in vivo antimalarial activities of pefloxacin and ciprofloxacin in swiss albino mice infected intravenously with 5 x 10(6) plasmodium yoelii n67 parasites 1 h before treatment. groups of 20 mice received a subcutaneous injection of 40, 80, or 160 mg of ciprofloxacin or pefloxacin per kg of body weight every 8 h for 3 days. parasitologic activity was assessed on day 4, and survival was assessed on day 21. control mice had a fulminant course with a parasitemia of 61.3% +/- 12.1 ...19901708223
glycolipid anchorage of plasmodium falciparum surface antigens.human red blood cells (rbc) were infected with the malarial parasite plasmodium falciparum, the anchoring of schizont proteins to rbc membranes by glycoinositol phospholipids was demonstrated by three criteria: (1) metabolic incorporation of 3h-ethanolamine and 3h-myristate into the protein; (2) release of 35s-methionine-labelled protein into the supernatant after incubation with phosphatidylinositol-specific phospholipase c; and (3) the exposure of a glycoinositol phosphate epitope on the methi ...19901708512
how to select plasmodium falciparum pre-erythrocytic antigens in an expression library without defined probe.the restricted access to plasmodium falciparum liver stages has greatly limited the analysis of the antigenic content of that stage. due to the lack of material to perform immunochemical studies, of access to mrna, and of monoclonal probes, we decided to screen a genomic library with stage-restricted human antibodies. this strategy led to the identification of a large number of dna fragments encoding both sporozoite specific as well as liver-stage specific epitopes. following the initial charact ...19901709833
active and passive immunization against plasmodium yoelii sporozoites.three subunit vaccines based on the major repeat, (qgpgap)n, and flanking regions of the plasmodium yoelii circumsporozoite protein were designed, produced, and tested. all were immunogenic, but none gave consistent protection against a 40-200 sporozoite challenge. to demonstrate that antibodies to p. yoelii cs protein could provide protection we established a passive transfer model. passive transfer of nys1, an igg3 mab against the p. yoelii cs protein, protected 100% of mice against challenge ...19901709834
the circumsporozoite protein of plasmodium: a mechanism of immune evasion by the malaria parasite?sporozoites of malaria are covered with a repetitive surface antigen, the circumsporozoite (cs) protein. this antigen also appears to be a major target of the host immune response. the natural immunogenicity of the cs protein has led to attempts to develop the molecule as a vaccine candidate. it seems paradoxical, however, that a successful parasite should present to the host an immunogenic surface molecule which would induce protective immunity. in this paper we suggest that the cs protein is n ...19901709835
evidence implicating mhc genes in the immunological nonresponsiveness to the plasmodium falciparum cs protein.the circumsporozoite (cs) protein is a major candidate vaccine antigen for the sporozoite stage of malaria. both cytotoxic t cells (ctl) and antibody specific for the cs protein are thought to be important in protection. by examining the immune response in mice and humans we have shown that genes mapping to the major histocompatibility complex (mhc) are important for immune responsiveness. f1 mice between high antibody responders and low antibody responders are high antibody responders, suggesti ...19901709836
an invariant, "universal" t-cell epitope in the p. falciparum circumsporozoite protein.although there are important obstacles to malaria vaccine development, we believe they might be overcome by a strategy of searching for conserved regions of a vaccine candidate that are recognized in association with many different hla molecules and, if necessary, deliberately modifying the conserved sequences to improve their immunogenicity for t cells. this approach is illustrated by work on the circumsporozoite (cs) protein of plasmodium falciparum, which covers the surface of the malaria spo ...19901709837
a ctl epitope on the circumsporozoite protein of p. yoelii.humans are infected with malaria by the bite of anophelene mosquitos carrying plasmodia sporozoites. these sporozoites pass quickly from the blood into hepatocytes, where they develop into mature liver-stage parasites over several days. the clinical stage of the illness begins only when the liver-stage parasites rupture into the bloodstream and erythrocytes are invaded. the pre-erythrocytic stages of malaria are inviting targets for vaccine development, because an effective immune response to th ...19901709838
disruption of plasmodium falciparum-infected erythrocyte cytoadherence to human melanoma cells with inhibitors of glycoprotein processing.adherence of plasmodium falciparum-infected erythrocytes (ie) to the venular endothelium in brain and other organs is characteristic of cerebral malaria, an often fatal complication in infected individuals. it has been shown that cytoadherence may be mediated through interaction of ie with glycoproteins on host target cell surfaces, including cd36 (gpiv), intercellular adhesion molecule-1 (icam-1), and thrombospondin. inhibitors of glycoprotein synthesis and processing were tested for their abil ...19911710120
acridine orange detection of plasmodium falciparum malaria: relationship between sensitivity and optical configuration.blood samples collected from five volunteers participating in a p. falciparum infectivity trial were examined to determine the efficacy of the acridine orange technique. several lens configurations were tested for efficiency in the diagnosis of malaria using this system. there was no significant difference in the sensitivity for detecting positive specimens or number of parasites among three lens configurations: a 50x long working distance objective (0.34 mm) with either a 10x ocular (total magn ...19911710424
epithelial membrane glycoprotein pas-iv is related to platelet glycoprotein iiib binding to thrombospondin but not to malaria-infected erythrocytes.glycoprotein (gp) iiib (also termed gpiv or cd36) is an integral platelet membrane protein, and has been identified as a binding site for thrombospondin, collagen, and malaria-infected erythrocytes. pas-iv is an integral membrane protein found in lactating mammary epithelial cells and capillary endothelial cells. the n-terminal sequence of pas-iv is nearly identical to that of gpiiib and monospecific anti-pas-iv antibody reacts with gpiiib, indicating that pas-iv is structurally related to gpiii ...19911710515
synthetic peptides for plasmodium vivax malaria sero-epidemiology. application of fmoc-polyamide and displacement chromatography.the immunodominant epitope of plasmodium vivax, one of the major causative agents of malaria in man, consists of the tandem repetitions of a nonapeptide sequence, aspargalaasp/alaglyglnproalagly, with asp (variant d) or ala (variant a), in the fourth position. synthetic peptides corresponding to the p. vivax epitope, containing a different number of nonapeptide sequences, were prepared by solid-phase synthesis according to the fmoc-polyamide method. three peptides, containing 1, 2, and 4 copies ...19911710611
failure of recombinant vaccinia viruses expressing plasmodium falciparum antigens to protect saimiri monkeys against malaria.saimiri sciurus monkeys were immunized at multiple sites with recombinant vaccinia viruses expressing plasmodium falciparum antigen genes and boosted 4 weeks later. control monkeys were immunized with a thymidine kinase-negative vaccinia virus mutant. two weeks later, all of the monkeys were challenged by intravenous inoculation of p. falciparum (indochina strain) parasites. a group of unimmunized monkeys was challenged in parallel. all of the monkeys that received vaccinia virus recombinants or ...19911711015
molecular basis of sequestration in severe and uncomplicated plasmodium falciparum malaria: differential adhesion of infected erythrocytes to cd36 and icam-1.the cd36 and icam-1 glycoproteins on vascular endothelial cells have been implicated as cytoadherence receptors for plasmodium falciparum-infected erythrocytes (irbc). adhesion of irbc from thai patients with uncomplicated and severe falciparum malaria to purified cd36 or icam-1 and to c32 melanoma cells was compared. all malaria isolates bound to solid phase-adsorbed cd36 and to fluid-phase 125i-labeled cd36. irbc adhesion to purified icam-1 varied widely, and no correlation with clinical sever ...19911711552
evaluation of the quantitative buffy coat (qbc) method to detect malaria-infected red blood cells.the conventional thin blood film method of detecting malaria is a long and tedious procedure, requiring significant technical expertise. in this study, we compared the quantitative buffy coat (qbc) capillary tube method, which requires only minimal technical training, to the thin blood film method, and found it to be not only more rapid but also more sensitive than the thin blood film method in the detection of parasitized red blood cells. we do not suggest that the qbc capillary method can repl ...19911711655
a novel cell surface trans-sialidase of trypanosoma cruzi generates a stage-specific epitope required for invasion of mammalian cells.when trypomastigotes of t. cruzi emerge from cells of the mammalian host, they contain little or no sialic acids on their surfaces. however, rapidly upon entering the circulation, they express a unique cell surface trans-sialidase activity. this enzyme specifically transfers alpha (2-3)-linked sialic acid from extrinsic host-derived macromolecules to parasite surface molecules, leading to the assembly of ssp-3, a trypomastigote-specific epitope. the t. cruzi trans-sialidase does not utilize cyti ...19911712251
role of intrastructural/intermolecular help in immunization with peptide-phospholipid complexes.the design of effective subunit vaccines requires the inclusion of both b and t cell epitopes. the best mechanism for including both types of epitopes within an ag is dependent upon how the ag is processed by the apc for presentation to a responsive th cell. if it is more efficient to process a single molecule for both helper and primary epitopes, than covalent linkage of b cells and t cell epitopes for intramolecular presentation of help would be recommended. if however, separate peptides conta ...19911712806
definition of the epitope recognized by the plasmodium falciparum-reactive human monoclonal antibody 33g2.the human monoclonal antibody 33g2 has earlier been shown to inhibit merozoite reinvasion of red blood cells in plasmodium falciparum cultures in vitro and to inhibit cytoadherence of infected red blood cells to melanoma cells in vitro. 33g2 cross-reacts with a family of p. falciparum antigens, ag332, pf11.1 and pf155/resa, sharing a common feature of repeated sequences consisting of regularly spaced pairs of glutamic acid. peptides corresponding to residues 2-19 of the known amino acid sequence ...19911712912
antibody responses to plasmodium falciparum gametocyte antigens during and after malaria attacks in schoolchildren from madang, papua new guinea.sera from 49 school children in madang, papua new guinea with malaria and follow-up sera from 40 of these cases were tested by competitive elisa for antibodies capable of inhibiting binding of eight monoclonal antibodies (moabs) to plasmodium falciparum gametocytes. the proportion of sera inhibiting each moab ranged from 31.2% to 85.7%. at follow-up, the proportion of inhibitory sera decreased for 3 moabs, did not change significantly for 4 moabs and increased for one moab. when sera were groupe ...19911712931
conserved and variant epitopes of target antigens of transmission-blocking antibodies among isolates of plasmodium falciparum from malaysia.monoclonal antibodies (mabs) directed against different epitope regions on three sexual stage-specific gamete surface proteins of plasmodium falciparum, pfs 25, pfs 230, and pfs 48/45, were used to study the genetic diversity of these epitopes among fresh isolates of p. falciparum from malaysia, using immunofluorescence microscopy (ifa). among 45 malaysian isolates, one epitope of pfs 25, designated region i, showed evidence of variable reactivity with mabs among different isolates; the pfs 25 e ...19911713424
plasmodium falciparum (human malaria)-induced modifications in human erythrocyte band 3 protein.a monoclonal antibody, 1c4, was produced which recognizes a 65 kda protein that is localized to the plasma membrane of human erythrocytes infected with plasmodium falciparum. by immunofluorescence the antigen was visualized as dots on the surface of the infected cell. the 65 kda protein was present in 4 strains of diverse geographical origin, and in erythrocytes infected with a knobless strain. the 65 kda protein was insoluble in non-ionic detergents, but was partly soluble in sds and some high ...19911714069
isotypic analysis, antigen specificity, and inhibitory function of maternally transmitted plasmodium falciparum-specific antibodies in gabonese newborns.an analysis of plasmodium falciparum-specific antibodies was performed in pairs of maternal and cord sera from gabon, a region endemic for malaria. all paired sera (n = 59) had p. falciparum-specific antibodies. immunofluorescence assays detected parasite-specific igg1, igg2, and igg3 in 100% of the tested pairs (n = 26) and igg4 in 42% of them. the titers of specific igg2 and igg3 were significantly lower in cord than in maternal sera. all maternal sera had specific igm. of the seven p. falcipa ...19911714245
immunity to sexual stages of human malaria parasites: immune modulation during natural infections, antigenic determinants, and the induction of transmission-blocking immunity.four antigens of plasmodium falciparum have so far been identified as targets of transmission-blocking antibodies; three of them (pfs 230, 48/45) are detectable in gametocytes and expressed on gametes, the fourth (pfs 25) appears only after fertilization. epitope analyses of each antigen were made with competitive immunoassays, and the extent of antigenic diversity determined amongst numerous isolates of p. falciparum. there was minimal variation within one of the two epitopes on pfs 230 both of ...19901714627
[antigenic diversity of asexual schizont antigen gp195 of plasmodium falciparum isolates from china].the antigenic diversity of asexual merozoite surface antigen precursor gp195 among 6 isolates of plasmodium falciparum from hainan and jiangsu provinces of china was investigated with a panel of murine anti-gp195 mcabs by indirect immunofluorescence assay and western blotting. the results show that all isolates express certain strain-common epitopes of gp195, and at the same time express or lack some strain-specific epitopes. the 6 isolates can be divided into two major gp195 serotypes according ...19911714800
h-2kd-restricted antigenic peptides share a simple binding motif.we have defined structural features that are apparently important for the binding of four different, unrelated antigenic epitopes to the same major histocompatibility complex (mhc) class i molecule, h-2kd. the four epitopes are recognized in the form of synthetic peptides by cytotoxic t lymphocytes of the appropriate specificity. by analysis of the relative potency of truncated peptides, we demonstrated that for each of the four epitopes, optimal antigenic activity was present in a peptide of 9 ...19911714934
direct access to serum macromolecules by intraerythrocytic malaria parasites.trafficking pathways in malaria-infected erythrocytes are complex because the internal parasite is separated from the serum by the erythrocyte and parasitophorous vacuolar membranes. intraerythrocytic plasmodium falciparum parasites can endocytose dextrans, protein a and an igg2a antibody. here we show that these macromolecules do not cross the erythrocyte or parasitophorous vacuolar membranes, but rather gain direct access to the aqueous space surrounding the parasite through a parasitophorous ...19911715521
generation of recombinant, carbohydrate-free intercellular adhesion molecule-1 (icam-1) and icam-1 fragments in escherichia coli and mapping of epitopes recognized by anti-icam-1 monoclonal antibodies.intercellular adhesion molecule-1 (icam-1) has been shown to interact with the integrin leukocyte function associated antigen-1 (lfa-1) in a variety of cell-cell adhesion phenomena. furthermore, it serves as a receptor for the majority of the rhinoviruses and for plasmodium falciparum-infected human erythrocytes. we generated recombinant, carbohydrate-free icam-1 and several icam-1 fragments by expression in escherichia coli using the fusion protein expression system puex1-3. in western blot and ...19911715847
[peptide synthesis--protein fragments from plasmodium falciparum and their conjugates with protein and synthetic carriers].to study coat proteins of plasmodium falciparum, seven putative antigenic-determinants of pmmsa, sharp, gbp and four known determinants of csp, cra and resa were synthesized. computerized methods for predicting protein antigenic determinants were employed to select the peptides. for immunochemical studies the peptides were conjugated to proteins and synthetic carriers by means of nonspecific and regiospecific heterobifunctional reagents.19911716102
[immunochemical study of antigenic determinants of surface protein s of the tropical malaria pathogen plasmodium falciparum using synthetic peptides].to develop new approaches to diagnostics and therapy of malaria, we carried out immunochemical study of the surface proteins of the tropical malaria parasite plasmodium falciparum with the use of synthetic peptides corresponding to the suggested antigenic determinants of the parasite proteins. rabbit antisera raised against the synthetic peptides bound to parasite proteins as shown by elisa and immunoblotting. affinity purified anti-peptide antibodies inhibited, in some cases, the parasite growt ...19911716103
location of human cytotoxic t cell epitopes within a polymorphic domain of the plasmodium falciparum circumsporozoite protein.studies in mice have shown that cytotoxic t lymphocytes (ctl) specific for epitopes within the circumsporozoite (cs) protein of malaria sporozoites can prevent malaria probably by destroying infected hepatocytes. this has provided a model for the development of a sporozoite vaccine. it has not been shown whether humans can mount a ctl response to this protein nor what determinants on the protein could be considered as target epitopes for such cells and thus merit inclusion in a sporozoite vaccin ...19911716144
cd8+ cytolytic t cell clones derived against the plasmodium yoelii circumsporozoite protein protect against malaria.immunization of balb/c mice with radiation-attenuated plasmodium yoelii sporozoites induces cytotoxic t lymphocytes (ctl) specific for an epitope located within the amino acid sequence 277-288 of the p. yoelii circumsporozoite (cs) protein. several cd8+ ctl clones were derived from the spleen cells of sporozoite-immunized mice, all displaying an apparently identical epitope specificity. all the clones induced high levels of cytolysis in vitro upon exposure to peptide-incubated mhc-compatible tar ...19911716146
prevention of murine cerebral malaria by a stable prostacyclin analog.iloprost, a synthetic prostacyclin analog, successfully prevents the development of cerebral malaria in mice. malaria antigen-induced tumor necrosis factor (tnf) production could be inhibited by iloprost in vitro and in vivo. northern analysis of tnf mrna revealed that malaria antigen-induced tnf expression was suppressed at the transcription level.19911716616
overcoming inhibition of antibody responses to a malaria recombinant vaccinia virus caused by prior exposure to wild type virus.pre-injection of mice with vaccinia virus inhibited the subsequent antibody response to a recombinant polypeptide expressed by vaccinia virus. the inhibition was overcome following additional challenges with recombinant vaccinia virus. this suggests that a potential disadvantage in vaccinia-immune individuals can be circumvented and may be outweighed by the advantages of the vector.19911716807
epitopes of the human malaria parasite p. falciparum carried on the surface of hbsag particles elicit an immune response against the parasite.the development of recombinant subunit vaccines against pathogenic organisms requires not only the identification of epitopes eliciting a protective immune response but also suitable carriers with adjuvant function. b- and t-cell epitopes of the malaria vaccine candidate gp190 were selected on the basis of a systematic search along the gp190 molecule and by computer prediction based on the amino acid sequence. using some of the epitopes identified, we have redesigned the surface of the hepatitis ...19911716808
model using a peptide with carrier function for vaccination against different pathogens.it has been shown that pre-immunization with a protein can inhibit the antibody response to a new b-cell sequence which is coupled to the protein (epitope-specific suppression). by utilizing a peptide with carrier function from the protein, rather than the entire protein, the antibody response to the new b-cell sequence is enhanced in protein-primed mice. the present results extend this observation by showing that mice which have been pre-immunized with a protein followed by a b-cell sequence li ...19911716809
human immune response in plasmodium falciparum malaria. synthetic peptides corresponding to known epitopes of the pf155/resa antigen induce production of parasite-specific antibodies in vitro.autologous cell mixtures containing t cells, b cells, and adherent accessory cells from individuals primed to the malaria parasite plasmodium falciparum by repeated natural infections were investigated for induction of ig and antibody secretion in vitro. in vitro activation of cell cultures with two synthetic peptides corresponding to immunodominant t cell epitopes of the merozoite ag ring-infected erythrocyte surface ag (mr 155,000) (pf155/resa), one from its carboxyl-terminal repeat and one fr ...19911717554
plasmodium falciparum reinfection in children from a holoendemic area in relation to seroreactivities against oligopeptides from different malaria antigens.the rate and densities of plasmodium falciparum reinfections were investigated in children five to 14 years old from one village in tanzania with a high transmission rate. initial parasitemias were eradicated by a curative treatment with quinine, a drug with a short elimination half-life, to minimize the effects of residual drug on reinfection. the seroreactivities to seven oligopeptides, representing t and b cell epitopes from the ring erythrocyte surface antigen (pf155/resa), the clustered arg ...19911718179
hla polymorphism and t cell recognition of a conserved region of p190, a malaria vaccine candidate.we have examined t cell recognition of a recombinant polypeptide (190l), corresponding to a 175-amino-acid-long conserved region of the major surface antigen (p190) of plasmodium falciparum merozoites. we show that 190l contains a variety of t cell epitopes, and can be recognized in association with many different mhc class ii molecules, including hla-dr, dp, and dq antigens. most of the epitope-containing peptides are able to bind to more than one dr, and a single dr molecule can bind to differ ...19911718405
in vivo effects of anti-idiotype on plasmodium chabaudi infection in mice.a polyclonal anti-idiotype was raised in rabbits following immunization with a murine monoclonal antibody which recognized a 250,000 mw antigen of plasmodium chabaudi-infected erythrocytes. the monoclonal antibody, nimp m23 (clone 3,) has been shown to protect mice against homologous parasite challenge. following purification, the anti-idiotype was shown to bind only the immunizing idiotype and to recognize antigen-binding site-associated anti-idiotype. mice primed with anti-idiotype and challen ...19911718854
a plasmodium falciparum malaria vaccine candidate which contains epitopes from the circumsporozoite protein and a blood stage antigen, 5.1.the previously described plasmodium falciparum blood stage antigen, 5.1 (also referred to as exp-1) was expressed at a high level in escherichia coli. saimiri monkeys immunised with purified recombinant antigen 5.1 were partially protected from p. falciparum blood stage parasite challenge. the gene coding for 5.1 was combined with dna coding for an (asn-ala-asn-pro)19 sequence (abbreviated (nanp)19 in the one-letter amino acid code). to facilitate purification of the recombinant protein, dna cod ...19911719416
population genetics of plasmodium falciparum within a malaria hyperendemic area.serotyping with monoclonal antibodies was used to estimate the number and frequencies of allelic variants of two merozoite surface proteins, msp1 and msp2, and an exported protein exp-1, in a sample of 344 clinical isolates of plasmodium falciparum from an urban region of the gambia. represented among the isolates were 36, 8 and 2 alleles of the msp1, msp2 and exp-1 loci respectively. relative frequencies of these alleles remained stable in the parasite population over the 2 years of the study. ...19911719468
[diseases observed after return from travels outside europe. 109 cases].we report a prospective study of travel-associated illnesses observed after their return in 109 french travellers, including 86 tourists. sixty-three were returning from africa and 84 percent had been abroad for less than 4 weeks. the percentages of travellers immunized against tetanus, poliomyelitis and typhoid fever were 70, 63 and 36 percent respectively. malaria prophylaxis was well adjusted to current recommendations in only 19 patients; for 9 patients it was a routine visit. one hundred pa ...19911719519
identification of a continuous and cross-reacting epitope for plasmodium falciparum transmission-blocking immunity.identification of continuous epitopes in the target antigens of plasmodium falciparum transmission-blocking antibodies is likely to facilitate the production of a subunit peptide vaccine. two such epitopes shared among several sexual-stage antigens were identified with murine monoclonal antibodies. an epitope recognized by four monoclonal antibodies capable of blocking infectivity of gametocytes in the mosquitoes is shared among three antigens (230, 48/45 doublet, and 27 kda). these antigens are ...19911719534
characterization of a plasmodium falciparum epitope recognized by a monoclonal antibody with broad isolate and species specificity. 19911719648
immunization of owl monkeys with a recombinant protein containing repeated epitopes of a plasmodium falciparum glycophorin-binding protein.a plasmodium falciparum glycophorin binding protein (gbp-130) has been implicated in protective immunity to malaria. the gene for gbp-130 encodes a protein containing 11 tandemly repetitive 50 amino acid units. we report an immunization trial in aotus monkeys using a recombinant dna protein containing three of these 50 amino acid repeats. when administered with aluminum hydroxide, this antigen induced low levels of antibodies that reacted with the recombinant protein by elisa and with parasite a ...19911719834
congenital malaria with chloroquine resistance.a preterm infant with possible congenital clinical malaria is described. the infant developed persistent pyrexia, hyperbilirubinaemia, anaemia, increasing gastric residuals and hepatosplenomegaly from the 7th day of life. thick and thin smears of the infant's blood were heavily loaded with various asexual stages of plasmodium falciparum. the parasite exhibited r1 resistance. there was no satisfactory response to chloroquine, but response to intravenous quinine therapy was achieved on day 15. the ...19911719926
adhesive functions of platelets lacking glycoprotein iv (cd36).glycoprotein iv (gpiv; cd36 or gpiiib) is a cell surface glycoprotein that has been proposed as mediating a number of physiologically important processes such as the adhesion of platelets to thrombospondin (tsp) and collagen, the cytoadherence of plasmodium falciparum-infected erythrocytes, and the tsp-dependent interaction of monocytes with platelets and macrophages. because platelets of the naka-negative phenotype have recently been shown to lack detectable gpiv, their availability offered the ...19911720035
plasmodium falciparum: intragenic recombination and nonrandom associations between polymorphic domains of the precursor to the major merozoite surface antigens.extensive allelic polymorphism in the plasmodium falciparum major merozoite antigen precursor (msp1/pmmsa) is partly due to intragenic recombination events within a short region near the 5' end of the gene. newly described allelic sequences from this region of the gene are compared to those previously published, revealing additional sites of intragenic recombination. epitopes recognised by monoclonal antibodies on the protein have been assigned on the basis of correlations between serology and a ...19911720396
multiple antigen peptides for specific detection of antibodies to a malaria antigen in human sera.multiple antigen peptides (map), consisting of a number of peptide copies synthesized on a branching lysyl core, offer a novel approach for rendering small peptides immunoreactive in solid-phase immunoassays. an octameric map, carrying 6 repeats of the sequence -n-a-a-g-, tandem repeated in the immunodominant region of the circumsporozoite (cs) protein of plasmodium malariae, was used as a model to evaluate the suitability of the map system in an indirect enzyme-linked immunosorbent assay (elisa ...19911720420
world malaria situation in 1989. part ii. 19911720650
persistence of cellular and humoral response to synthetic peptides from defined plasmodium falciparum antigens.the cellular and humoral immune responses to synthetic peptides reproducing the repeat sequences of two major vaccine candidates (circumsporozoite protein and pfl55/resa) were investigated in two groups of african subjects according to the length of their stay outside endemic areas. the relation between the lymphoproliferative response and the antibody levels to these antigens was studied. the results confirm the existence of t-cell epitopes within the repeat sequences of the cs protein and the ...19911720947
immunogenicity of multiple antigen peptides (map) containing t and b cell epitopes of the repeat region of the p. falciparum circumsporozoite protein.the immunogenicity of multiple antigen peptides (map) constructs containing t and b cell epitopes of the repeat region of the p. falciparum circumsporozoite (cs) protein was examined in vitro, using a human t cell clone, and in vivo, using four different strains of mice. all the map constructs that contained the t cell epitope, (dpnanpnvdpnanpnv), stimulated proliferation and interferon-gamma production by a human t cell clone specific for this epitope which is located in the 5' end of the repea ...19911721025
towards the design of heterovalent anti-malaria vaccines: a hybrid immunogen capable of eliciting immune responses to epitopes of circumsporozoite antigens from two different species of the malaria parasite, plasmodium.the peptide cs.t3, corresponding to residues 378-398 of the plasmodium falciparum (pf) circumsporozoite (cs) protein sequence (except with cysteines 384 and 389 replaced by alanines), has been found to be almost universally recognized by human and mouse t lymphocytes. when colinearly linked to the repetitive b-lymphocyte-specific epitope (asn-ala-asn-pro)n of pf cs protein, cs.t3 induces t-helper activity for an anti-(asn-ala-asn-pro)n antibody response in mice of different haplotypes. we constr ...19911721043
failure to detect mhc class ii associations of the human immune response induced by repeated malaria infections to the plasmodium falciparum antigen pf155/resa.available evidence suggests that human t and b cell responses to a major plasmodium falciparum malaria antigen (pf155/resa) in individuals primed by repeated infections are genetically regulated. in the present study we have attempted to establish whether these regulations reflect genetic restrictions imposed on the immune response by class ii molecules of the donor's mhc system. t cell activation (proliferation and ifn-gamma release in vitro) and antibody activity (elisa) were assayed with synt ...19911721833
cytotoxic cd4+ t cells from a sporozoite-immunized volunteer recognize the plasmodium falciparum cs protein.the present data provide the first evidence that a protozoan parasite, plasmodium falciparum, can induce cd4+ cytotoxic t cells in man. the cd4+ cytotoxic t lymphocytes (ctl) were derived from a sporozoite-immunized volunteer who was protected against challenge with p. falciparum sporozoites. these t cells recognize an epitope within the circumsporozoite (cs) protein, an immunodominant sporozoite surface antigen, present also in liver stages of the parasite, which has been investigated as a vacc ...19911721837
selection of t cell epitopes and vaccine engineering. 19911722274
stage-specific expression of plasmodial proteins containing an antigenic marker of the intraerythrocytic cisternae.a monoclonal antibody, lwli, recognized 3 proteins of 45, 50 and 102 kda in plasmodium falciparum-infected erythrocytes. the 45- and 50-kda proteins were parasite-encoded and displayed markedly different peptide maps, indicating that they were distinct plasmodial polypeptides with a common antigenic epitope rather than differentially processed forms of a primary translational product. the 45-kda protein was present throughout intraerythrocytic growth, while the 50-kda molecule was not detected e ...19911723147
processing of the plasmodium falciparum major merozoite surface protein-1: identification of a 33-kilodalton secondary processing product which is shed prior to erythrocyte invasion.we have previously shown that only a single 19-kda fragment of the plasmodium falciparum major merozoite surface protein (msp1) is carried with an invading merozoite into the infected red cell. this fragment (msp1(19] is derived from the c-terminal membrane-bound end of a major product, msp1(42), of the primary stage of msp1 proteolytic processing. using a monoclonal antibody mapped to an epitope within the n-terminal region of msp1(42), we have shown that a soluble 33-kda polypeptide (msp1(33) ...19911723148
identification of a common plasmodium epitope (cpe) recognised by a pan-specific inhibitory monoclonal antibody.a plasmodium falciparum genomic expression library was screened with a monoclonal antibody produced from mice infected with plasmodium yoelii. eleven unique clones were isolated all of which contained the sequence nknd, iknd or kknd. this sequence was confirmed as the epitope of m26-32 by testing a series of overlapping peptides and the allowable substitutions determined by testing the binding of m26-32 to peptides containing all possible single amino acid replacements of nknd. potential epitope ...19911723149
[use of synthetic carriers and adjuvants for increasing the immunogenicity of a synthetic peptide from the cs-protein of plasmodium falciparum].in order to increase immunogenicity of the peptide (nanp)3, we have prepared a large set of fully synthetic constructions based on the peptide, glycopeptide adjuvant gmdp and some synthetic carriers. immunogenicity of these constructions was tested on mice (line c57b1/6) responding to the peptide polymer (nanp)40 without carrier and on mice (line balb/c) not responding to this antigen. immunogenic constructions based on synthetic polytuftsin induced as high titres of anti-(nanp)3 antibodies as t ...19911723268
african trypanosomes express an immunogenic protein with a repeating epitope of 24 amino acids.infection with intracellular protozoan parasites such as plasmodium, leishmania and trypanosoma cruzi induces a strong antibody response against proteins containing tandem repeats, suggesting that these repetitive epitopes may camouflage vulnerable parasite antigens from a 'protective' immune response. we tested this theory by immunoscreening a cdna expression library of african trypanosomes, extracellular parasites that evade their hosts' immune response by antigenic variation, and found that t ...19911723507
detection of different developmental stages of malaria parasites by non-radioactive dna in situ hybridization.a highly sensitive non-radioactive dna in situ hybridization procedure is described that enables detection and unequivocal identification of various developmental stages of human and rodent malaria parasites. using biotinylated species-specific dna probes, erythrocytic parasites can be specifically stained in blood smears. similarly exoerythrocytic stages can be visualized in cell culture and in sections of paraffin-embedded liver. in blood smears, the hybridization procedure provides a rapid de ...19911723723
[use a of dna probe to detect cellular immunity against intracellular parasitism].by using a specific, repetitive dna probe, we have been able to detect picograms of p. berghei dna. with this probe we have determined that: a) p. berghei, inoculated into norway brown rats, reaches its peak of proliferation in the liver 44 h after infection; b) gamma interferon inhibits in a dose-dependent fashion the development of liver exoerythrocytic forms (eef) in vivo and in vitro, and; c) endogenous gamma interferon inhibits the development of eef in hosts immunized with irradiated sporo ...19901723869
antigenic analysis of plasmodium yoelii liver stages by fluorescence antibody assays.little is known about the immune response against liver stage antigens which were first described for plasmodium falciparum. in order to provide a basis for experimental studies, we analysed antigenically the liver stages of plasmodium yoelii using sera of restricted specificity. several distinct fluorescence patterns could be described in maturing liver forms. one pattern was identified as corresponding to antigens specific to the liver phase which are also species specific. another pattern cor ...19911724570
peptide immunization can elicit malaria protein-specific memory helper but not proliferative t cells.we have studied the proliferative and helper t cell responses in mice to a malaria sporozoite vaccine candidate currently undergoing human trials. following immunization of b10 (i-ab) mice with the purified recombinant baculovirus-expressed plasmodium falciparum circumsporozoite protein, draining lymph node cells were challenged in vitro with a series of overlapping synthetic peptides which span the construct. surprisingly, only a single peptide from the protein was immunodominant in that it cou ...19901724615
[applications of q beta replicase for diagnostic purposes]. 19911724730
epitopes of the plasmodium falciparum clustered-asparagine-rich protein (carp) recognized by human t-cells and antibodies.linear b- and t-cell epitopes have been identified in the plasmodium falciparum clustered-asparagine-rich-protein (carp). twenty-six synthetic peptides, 15-25 amino acids in length, were assayed for their ability to stimulate purified, human t-cells primed to p.falciparum by natural infection to proliferate and/or secrete gamma-interferon (ifn gamma). the plasma of malaria exposed individuals were tested for antibody reactivity with peptides coupled to bovine serum albumin in a semiquantitative ...19911725821
cross-reacting epitopes shared between plasmodium falciparum and its host: the origin of autoreactive antibodies? 19911726272
heat shock proteins as "super"-carriers for sporozoite peptide vaccines? 19911726273
possible mechanisms for the maintenance of polymorphisms in plasmodium populations.there are two views on the origin and maintenance of the high levels of polymorphism found in antigenic plasmodium proteins. immune selectionists consider that mutations which avoid stimulating a host response are frequent and advantageous. proponents of the random genetic drift of selectively equivalent mutations hold that plasmodium antigens are relatively unconstrained and can tolerate considerable structural diversity. both sides agree that antigenic diversity is advantageous although select ...19911726483
il-6 induced by il-1 inhibits malaria pre-erythrocytic stages but its secretion is down-regulated by the parasite.the capacity of il-6 to mediate the antiparasitic activity of il-1 on intrahepatic development of malaria parasite was demonstrated. the comparisons of il-6 levels in infected and noninfected hepatocyte cultures, either purified or enriched with nonparenchymal cells and stimulated by il-1 or il-6, indicate that subtle interactions exist between intrahepatocytic development of plasmodium yoelii and liver synthesis of il-6. during its intrahepatic multiplication, the parasite causes a decline in i ...19921727866
protective immunization with invariant peptides of the plasmodium falciparum antigen msa2.three octapeptides from the n and c terminal c regions of the merozoite surface ag 2 (msa2) of plasmodium falciparum elicit anti-msa2 antibody when given as diphtheria toxoid conjugates. these antibodies also bind to the msa2 homolog from the rodent malaria plasmodium berghei. all mice vaccinated with these conjugates and challenged with an otherwise lethal inoculum of p. berghei showed substantial protection with most surviving. there was a inverse correlation between the development of the par ...19921727867
t-cell-dependent immunity and thrombocytopenia in rats infected with plasmodium chabaudi.normal, splenectomized, and athymic fischer rats were infected with plasmodium chabaudi. in normal rat infections, acute-phase infection resolved rapidly and completely. in splenectomized rats, infection resulted in high parasitemia and ultimately death. in nude rats, parasite growth was reduced compared with normal rats, and a persistent parasitemia (between 20 and 45%) was observed for several months. complete resolution of the infection was achieved after adoptive transfer of t lymphocytes, e ...19921729178
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