Publications

plasmodium falciparum: elicitation by peptides and recombinant circumsporozoite proteins of circulating mouse antibodies inhibiting sporozoite invasion of hepatoma cells.	the immunodominant epitope region of the circumsporozoite protein of plasmodium falciparum sporozoites contains 37 tandem repeats of the tetrapeptide asn-ala-asn-pro and 4 repeats of asn-val-asp-pro. synthetic peptides and recombinant proteins of the repeat region were used to immunize mice using different doses and adjuvants. antisera were tested for inhibition of sporozoite invasion of cultured human hepatoma cells. synthetic peptides and recombinant proteins elicited high levels of antibodies ...	1987	2438152
host immune response and pathological expression in malaria: possible implications for malaria vaccines.		1987	2438630
development of immunity in natural plasmodium falciparum malaria: antibodies to the falciparum sporozoite vaccine 1 antigen (r32tet32).	antibodies that reacted with a candidate sporozoite vaccine antigen (r32tet32) were found in 20 of 21 patients treated for acute infection with plasmodium falciparum and monitored longitudinally over 67 days. r32tet32 contains 32 tandem copies of a tetrapeptide sequence that constitutes the immunodominant epitope of the circumsporozoite surface protein. the magnitude of the antibody response varied considerably among individuals and appeared to be independent of the number of previous clinical i ...	1987	2439533
safety and immunogenicity in man of a synthetic peptide malaria vaccine against plasmodium falciparum sporozoites.	a 12 amino-acid synthetic peptide (nanp)3 comprising the immunodominant epitope of plasmodium falciparum circumsporozoite protein was conjugated to tetanus toxoid (tt), adjuvanted with aluminium hydroxide, and administered intramuscularly in three doses at monthly intervals to 35 healthy males as a malaria vaccine. no significant adverse reactions were noted, with mild soreness at the injection site the only common symptom. seroconversions against nanp occurred in 53% and 71% of recipients of 10 ...	1987	2439920
detection of antibodies in human sera to the repeating epitope of the circumsporozoite protein of plasmodium falciparum using the synthetic peptide (nanp)3 in an enzyme-linked immunosorbent assay (elisa).	an enzyme-linked immunosorbent assay (elisa) was developed to detect antibody in human sera to a synthetic peptide, asn-ala-asn-pro (nanp)3, derived from the repeating amino acid sequence found in the surface circumsporozoite protein of plasmodium falciparum sporozoites. one hundred four sera from u.s. residents were used to determine a cut-off value for reactivity. test sera were considered reactive when the absorbance was greater than that at the 95th percentile of the control sera. sera from ...	1987	2440327
polypeptide antigens mr 90,000 and 72,000 related to protective immunity against the blood form of plasmodium falciparum in the squirrel monkey show stable characteristics in strains from different geographic origins.	squirrel monkeys protected after vaccination with a particular protein fraction of plasmodium falciparum elicit antibodies directed against two parasite proteins, mr 90,000 and 72,000. we have used monoclonal antibodies and sera from protected monkeys to determine whether or not these polypeptides were polymorphic in 22 strains. in all the isolates studied, both polypeptides were conserved, as was the epitope defined by monoclonal antibody xiv/7 present on the mr 90,000. immunofluorescence of al ...	1987	2440330
plasmodium falciparum: sporozoite boosting of immunity due to a t-cell epitope on a sporozoite vaccine.	plasmodium falciparum: sporozoite boosting of immunity due to a t-cell epitope on a sporozoite vaccine. experimental parasitology 64, 64-70. the impact of a malaria sporozoite vaccine may be enhanced if protective immunity elicited by the vaccine is boosted by natural exposure to sporozoites. for this to occur, a helper t lymphocyte epitope present on the vaccine must be shared by sporozoites. these studies show that t cells from mice immunized with r32tet32, the plasmodium falciparum sporozoite ...	1987	2440712
clinical profile of malaria in children--a prospective study from aligarh (n. india).	in a prospective, hospital-based study in north india, malaria accounted for 1.5% of paediatric outpatient attendances during 1 year. a marked increase in the prevalence of malaria was noted during the post-monsoon months. plasmodium falciparum was the causative species in 44.4% of cases, contrary to previous reports of low prevalence of this parasite in the area. pyrexia with or without chills or rigor, vomiting, pallor and hepatosplenomegaly were the common presenting clinical features. spleni ...	1987	2441656
sequence variation in putative functional domains of the circumsporozoite protein of plasmodium falciparum. implications for vaccine development.	sequences of the circumsporozoite protein gene from five isolates of the human malaria parasite plasmodium falciparum are compared, and the extent of sequence variability within putative functional domains is assessed in terms relating to vaccine efficacy. nucleotide substitutions were observed outside of the immunodominant domain. of the substitutions observed outside of the repeat domain, none were silent. the substitutions correlated with biologically functional regions, such as a helper t ce ...	1987	2442154
antigenic analysis of the repeat domain of the circumsporozoite protein of plasmodium vivax.	in the present study we analyzed the fine specificity of mouse monoclonal and human polyclonal antibodies directed against the repeat domain of the circumsporozoite (cs) protein of the human malaria parasite, plasmodium vivax. five synthetic peptides, representing monomeric and dimeric repeats of this malarial antigen, were assayed for their capacity to inhibit the binding of these antibodies to a yeast-derived recombinant cs protein. the results revealed the existence of at least two distinct r ...	1987	2442254
plasmodium falciparum: hoechst dye 33258-cscl ultracentrifugation for separating parasite and host dnas.		1987	2443383
vital staining of plasmodium falciparum with cationic fluorescent rhodamine dyes.		1987	2443630
enhanced epitopic response to a synthetic human malarial peptide by preimmunization with tetanus toxoid carrier.	successful human vaccination by synthetic malarial sporozoite peptides may depend on the choice of an appropriate carrier. tetanus toxoid (tt) has been proposed because of its safe and widespread use in humans. paradoxically, however, prior exposure to this toxoid vaccine could produce specific epitopic suppression against synthetic malarial peptides conjugated to this same protein as carrier. indeed, we have previously reported that such a phenomenon can occur in the case of a synthetic vaccine ...	1987	2444539
structure of the fira gene of plasmodium falciparum.	the falciparum interspersed repeat antigen (fira) plays a dominant role in the human antibody response to the malaria parasite plasmodium falciparum. we have therefore determined the complete sequence of a genomic clone encoding fira. the fira gene contains a single intervening sequence, located immediately 3' to the putative hydrophobic core of a signal sequence in the short (100 amino acids) exon 1. the second exon largely encodes blocks of 13 hexapeptide repeats based loosely on the consensus ...	1987	2444858
localization of plasmodium falciparum histidine-rich protein 1 in the erythrocyte skeleton under knobs.	plasmodium falciparum parasites that induce knobs in the host erythrocyte membrane (k+ phenotype) synthesize a 90 kda histidine-rich protein (pfhrp-1), whereas knobless variants do not. a monoclonal antibody (mab 89) to pfhrp-1, in combination with cryo-thin section immunoelectron microscopy, localized the antigen in the parasitophorous vacuolar space and vesicles within the erythrocyte cytosol. additional immunoelectron microscopic studies showed that pfhrp-1 was also associated with submembran ...	1987	2444884
cloning and characterization of an abundant plasmodium knowlesi antigen which cross reacts with gambian sera.	a 110 kda plasmodium knowlesi antigen, termed pk110, has been identified on the basis of messenger rna abundance in late schizonts. most plasmodium genes previously cloned have been identified by immune sera, which have selected immunodominant antigens composed of repeating epitopes. although pk110 was not selected by immune sera, it also contains amino acid repeats, indicating that this structure may be a common feature of malarial proteins. determination of 296 codons in the pk110 gene reveale ...	1987	2444886
genetic studies on malaria parasites.		1985	2444919
[advances in the development of a malaria vaccine].		1987	2445538
[value of rapid diagnosis of plasmodium falciparum using indirect monoclonal immunofluorescence].	development and use of murine specific monoclonal antibodies associated with an indirect immunofluorescent assay allows a rapid detection of p. falciparum antigens. this work compares the results obtained by interpretation of giemsa staining technique on blood smears, to the use of a commercial reagent (monofluo kit p. falciparum). this monoclonal indirect immunofluorescent assay (i.f.i.m.) provides the clinician with a precious aid to diagnosis as well by its specificity and sensitivity, better ...	1987	2446789
inhibitory activity of interferons and interleukin 1 on the development of plasmodium falciparum in human hepatocyte cultures.	we have studied the effect of natural and recombinant human interferons (huifn-alpha, -beta, and -gamma), and interleukin 1 (il-1) on development of sporozoites of plasmodium falciparum in cultures of functional hepatocytes. huifn-gamma inhibits hepatic schizogony of p. falciparum at very low concentrations (0.1 to 10 international units/ml), the target being the hepatocyte. application after sporozoite inoculation is effective, suggesting an intracellular mechanism. there is also an 84% inhibit ...	1987	2447163
the 230-kda gamete surface protein of plasmodium falciparum is also a target for transmission-blocking antibodies.	immunization with extracellular sexual stages of the malaria parasites can induce the production of antibodies which block the development of the parasites in the midgut of a mosquito after a blood meal. we have generated a number of monoclonal antibodies against gametes and zygotes of the human malaria plasmodium falciparum. two monoclonal antibodies (mab) reacting with a 230-kda gamete surface protein (mab 1b3 and 2b4 both isotype igg2a) were found to block transmission of p. falciparum to mos ...	1987	2447164
inhibitory monoclonal antibodies to soluble plasmodium falciparum antigens.	several murine monoclonal antibodies were raised against purified soluble plasmodium falciparum antigens from the asexual blood stage. the monoclonal antibodies were purified from ascites by preparative agarose gel electrophoresis and tested for inhibitory activities against p. falciparum in vitro cultures. one monoclonal antibody, hatr 2-4, showed an isolate-specific growth inhibition of p. falciparum in vitro cultures. the antibody reacted in immunoblotting with bands of 250 and 57 kilo dalton ...	1987	2447580
invasion of red blood cells by malaria parasites--what are the components that determine specificity?		1986	2447821
absence of antigenic diversity in pf155, a major parasite antigen in membranes of erythrocytes infected with plasmodium falciparum.	pf155 is a merozoite-derived polypeptide antigen which the parasite plasmodium falciparum deposits in the membranes of erythrocytes at invasion. eleven laboratory strains or clones of p. falciparum and a large number of isolates obtained from patients from different parts of the world were studied for antigenic diversity in pf155. immunoglobulin g antibodies from different serum samples from p. falciparum-infected donors were affinity purified on monolayers of glutaraldehyde-fixed and air-dried ...	1987	2448335
structure and expression of the knob-associated histidine-rich protein of plasmodium falciparum.	cdna clones encoding 473 amino acids of the knob-associated histidine-rich protein (pfhrpi) of plasmodium falciparum clone fcr-3/a2 (gambia) have been isolated and sequenced. although a short region close to the amino terminus of the predicted sequence contains three blocks of six, seven or nine consecutive histidine residues, the most abundant amino acid is lysine. the predicted sequence contains a putative amino-terminal signal sequence and two potential asparagine glycosylation sites. a 1284 ...	1987	2448620
characterization of gp195 processed products purified from plasmodium falciparum culture supernates.	schizonts of the malaria parasite plasmodium falciparum synthesize a 195 kda surface glycoprotein (gp195) that is processed into several smaller products including one of 83 kda, which, in the case of the camp strain, is sequentially processed into 73 and 67 kda products. gp195 and its processing intermediates larger than 83 kda were not precipitated from culture supernates, but the 83 and 73 kda products were precipitated by three monoclonal antibodies (mcabs). the 83 and 73 kda products were a ...	1987	2448621
the primary structure of a plasmodium falciparum polypeptide related to heat shock proteins.	a cdna library constructed from ring-stage rna isolated from plasmodium falciparum fcr-3/gambia was screened with immune human serum and two related positive clones were isolated. nucleotide sequence analysis of these recombinant clones revealed an open translational reading frame for 681 amino acids with a calculated molecular weight of 74.3 kda. the deduced amino acid sequence of the polypeptide shows extensive homology to several heat shock proteins (hsp) which have been described. northern a ...	1987	2448622
giardia intestinalis antigens expressed in escherichia coli.	cdna and genomic dna of giardia intestinalis have been cloned in puc vectors and used to express giardia antigens in escherichia coli. several expression libraries have been produced and positive clones identified by immuno-colony assays with antisera raised against whole parasites and partially purified antigen(s). those clones which express g. intestinalis antigens have been used to raise antisera in mice and the antisera used in immunofluorescence assays. the proteins expressed by the clones ...	1987	2448623
topography of epitopes on a polymorphic schizont antigen of plasmodium falciparum determined by the binding of monoclonal antibodies in a two-site radioimmunoassay.	the topographic distribution of common and variant epitopes on two divergent allelic forms of the 185-205k schizont glycoprotein of plasmodium falciparum were studied by a two-site radioimmunoassay using monoclonal antibodies. similarities in the conformation of the two molecules were apparent. on both antigens two distinct regions were mapped, each comprising of both strain-common and polymorphic epitopes. epitopes common to the two psas were found to be closely associated with different variab ...	1987	2448732
the 3' portion of the gene for a plasmodium yoelii merozoite surface antigen encodes the epitope recognized by a protective monoclonal antibody.	the 230-kda merozoite antigen of the murine malarial parasite plasmodium yoelii provides a potential model system for the development of a protective erythrocytic stage vaccine. to characterize this antigen at the molecular level, isolated p. yoelii 17xl dna was used to construct a genomic library in the expression vector lambda gt11. a monoclonal antibody, mab 302, which passively protected mice against p. yoelii challenge infection, was used to identify a lambda gt11 recombinant clone encoding ...	1988	2448778
human t-cell recognition of the circumsporozoite protein of plasmodium falciparum: immunodominant t-cell domains map to the polymorphic regions of the molecule.	the definition of human t-cell antigenic sites is important for subunit vaccine development of a peptide immunogen if the goal is to allow antibody boosting during infection or to stimulate antibody-independent t-cell immunity. to identify such sites on the circumsporozoite (cs) protein of plasmodium falciparum, 29 overlapping synthetic peptides spanning the entire cs protein were made and tested for their ability to stimulate peripheral blood lymphocytes from 35 adults living in a p. falciparum ...	1988	2448793
murine monoclonal antibodies associated with rh17, rh29, and rh46 antigens.	after immunization with native human red cells and red cells infected with plasmodium falciparum, mouse splenocytes were fused with a myeloma cell line to obtain hybridomas. among the antibodies specific for blood group antigens, four antibodies (ib3c4, f12, mr432, and ib4) directed against epitopes related to the rh antigen were selected for characterization. it is suggested that two monoclonal antibodies (ib3c4 and f12) recognized an epitope associated with the rh29 antigen. the specificity of ...	1988	2448930
plasmodium falciparum sequestration: okm5 antigen (cd36) mediates cytoadherence of parasitized erythrocytes to a myelomonocytic cell line.		1988	2449507
variation in the precursor to the major merozoite surface antigens of plasmodium falciparum.	the major antigens on the surface of plasmodium falciparum merozoites are derived from a single high molecular weight polypeptide. the precursor to the major merozoite surface antigen (pmmsa) has conserved and variable antigenic determinants and varies in size in different isolates. since the protein is a candidate for a malaria vaccine, it is important to understand the molecular basis of this variation. we present the complete sequence of the pmmsa of the papua new guinea isolate fc27 and the ...	1988	2449612
immunologic modeling of a 75-kda malarial protein with carrier-free synthetic peptides.	a protein of 75 kda is produced in large quantities by the human malarial parasite plasmodium falciparum and is present on the surface of the merozoite, whose function is to infect erythrocytes. based on nucleotide sequence coding for 40% of this protein, two nonoverlapping model peptides 13 and 19 residues long were synthesized, coupled to a keyhole limpet hemocyanin carrier, and used to immunize rabbits. although both antisera had high titers of anti-peptide antibodies, only that raised agains ...	1988	2449696
enhancement of human natural cytotoxicity by plasmodium falciparum antigen activated lymphocytes.	mononuclear cells (mnc) isolated from malaria immune donors and from donors never exposed to malaria were stimulated in vitro with soluble purified plasmodium falciparum antigens (spag) or ppd. after 7 days of culture the proliferative response and the cytotoxic activity against the natural killer cell (nk cell) sensitive cell line, k562, were measured. it was found that spag stimulation enhanced cytotoxic activity of mnc from donors whose lymphocytes exhibited a strong proliferative response to ...	1987	2449809
immunogenicity and epitope mapping of foreign sequences via genetically engineered filamentous phage.	repeat regions of the circumsporozoite protein gene of plasmodium falciparum were cloned into the piii gene of a filamentous phage. these genetically engineered filamentous phage display the recombinant proteins on their surface. we demonstrate that they are both antigenic and immunogenic in rabbits. the recombinant phage were shown to be useful as a source of antigen for this scarce malaria protein, for producing carrier-hapten conjugates for obtaining immunological reagents in rabbits, and for ...	1988	2450091
a synthetic vaccine protects humans against challenge with asexual blood stages of plasmodium falciparum malaria.	we have previously shown that a mixture of three synthetic peptides (83.1, 55.1, 35.1), corresponding to fragments of the relative molecular mass 83,000 (83k), 55k and 35k plasmodium falciparum merozoite-specific proteins, induces protection in aotus triviroatus monkeys experimentally infected with p. falciparum. here we describe two polymeric synthetic hybrid proteins based on these peptides that delay or suppress the development of parasitaemia in immunized human volunteers.	1988	2450281
immunogenicity of a non-repetitive sequence of plasmodium falciparum circumsporozoite protein in man and mice.	in the present work, the hypothesis that individuals naturally exposed to plasmodium falciparum malaria infection in endemic areas produce antibodies directed against non-repetitive epitopes of the circumsporozoite protein was investigated. using a synthetic peptide reproducing the non-repetitive group-conserved region i sequence, we have shown that specific anti-region i antibodies are detectable in sera from endemic countries. of these sera, 87% also had antibodies against the immunodominant r ...	1988	2450833
major surface antigen p190 of plasmodium falciparum: detection of common epitopes present in a variety of plasmodia isolates.	plasmodium falciparum merozoites are covered with polymorphic proteins that are processed from a 190 kd (p190) precursor protein. these are candidates for an antimalarial vaccine. we cloned and expressed a number of dna fragments, comprising almost the entire p190 gene of the k1 isolate, in escherichia coli. pooled human endemic-area sera and rabbit antibodies raised against p190 protein isolated from k1 parasites react with only a limited number of the recombinant proteins. from these studies w ...	1988	2452082
nonpolymorphic regions of p190, a protein of the plasmodium falciparum erythrocytic stage, contain both t and b cell epitopes.	two conserved regions from the genetically polymorphic p190 molecule of the malaria parasite plasmodium falciparum have previously been expressed in escherichia coli as separate polypeptides (190.l and 190.m) or as a single fusion protein (190.n). in the present study we investigated whether human b and t lymphocytes recognize these conserved regions. the more amino-terminal region, 190.l (corresponding to residues 188-363 of the encoded protein sequence) reacted preferentially with sera from do ...	1988	2452192
neonatal exposure to immunogenic peptides. differential susceptibility to tolerance induction of helper t cells and b cells reactive to malarial circumsporozoite peptide epitopes.	the effects of neonatal administration of immunogenic peptides on subsequent t and b cell function were tested using defined t and b cell peptide epitopes from the circumsporozoite (cs) protein of the human malaria parasite, plasmodium falciparum. we observed that neonatal exposure of responder strain mice to either of the two major murine t sites on the cs protein resulted in specific tolerance of both helper and proliferating t cells. one of these t sites, (nanp)n, is also the immunodominant b ...	1988	2452193
proteosome-lipopeptide vaccines: enhancement of immunogenicity for malaria cs peptides.	proteosomes are hydrophobic, membranous, multimolecular preparations of meningococcal outer membrane proteins that are also b cell mitogens. these characteristics suggested that proteosomes may serve as carrier proteins and adjuvants to enhance peptide immunogenicity. although high titers of malaria circumsporozoite (cs) antibodies protect against malaria, vaccines thus far tested in humans have been insufficiently immunogenic to be clinically useful. here it is shown that synthetic cs peptides ...	1988	2452484
epitopes recognized by human t lymphocytes on malaria circumsporozoite protein.	the circumsporozoite protein of the malaria parasite plasmodium falciparum contains regions of nonrepetitive sequences which are predicted to be t cell recognition sites. we synthesized peptides corresponding to three of these regions, and tested their ability to stimulate proliferation of peripheral blood lymphocytes from donors living in a malaria-endemic area, or from nonimmune donors. cells from 15 out of 22 donors (including 4 of 6 nonimmune individuals) were stimulated by one or more of th ...	1988	2452748
an antigenic complex in the rhoptries of plasmodium falciparum.	a previously identified putative rhoptry antigen of plasmodium falciparum is composed of two major components, one of 80 kda and a doublet at 42/40 kda. an inhibitory monoclonal antibody immunoprecipitated both the 80 kda protein and the 42/40 kda doublet, but immunoblotted only the 80 kda component. a second monoclonal antibody, raised against the affinity purified complex, immunoblotted only the 42 kda band under non-reducing conditions. electron microscopic examination of thin sections of par ...	1988	2452978
characterization by anti-ig monoclonal antibodies of protective and non-protective antibodies against asexual forms of plasmodium falciparum in the saimiri monkey.	four monoclonal antibodies (mab) which recognize distinct epitopes on saimiri immunoglobulins were successfully used to characterize the protective and non-protective antibodies developed by this experimental host in response to infection by the human malaria parasite plasmodium falciparum. two of these mab, 3f11/g10 and 3e4/h8, were igg-specific and directed against conformationally conserved epitopes on the intact molecule. mab 3a2/g6 and 4g3/b5 were specific for epitopes on two distinct l cha ...	1987	2453202
plasmodium chabaudi antigen pch105, plasmodium falciparum antigen pf155, and erythrocyte band 3 share cross-reactive epitopes.	by immunoblotting with a number of monoclonal antibodies raised in human and murine malaria systems, we have been able to establish the presence of cross-reactive epitopes on the plasmodium falciparum vaccine candidate antigen pf155/resa and its proposed plasmodium chabaudi analog pch105. these findings were confirmed when the same antibodies were tested in an immunofluorescence assay. by using short synthetic peptides corresponding to repeated sequences in the c terminus of the pf155 and enzyme ...	1988	2453468
secretion of plasmodium falciparum rhoptry protein into the plasma membrane of host erythrocytes.	the rhoptry is an organelle of the malarial merozoite which has been suggested to play a role in parasite invasion of its host cell, the erythrocyte. a monoclonal antibody selected for reactivity with this organelle identifies a parasite synthesized protein of 110 kd. from biosynthetic labeling experiments it was demonstrated that the protein is synthesized midway through the erythrocytic cycle (the trophozoite stage) but immunofluorescence indicates the protein is not localized in the organelle ...	1988	2453514
an epitope recognised by inhibitory monoclonal antibodies that react with a 51 kilodalton merozoite surface antigen in plasmodium falciparum.	monoclonal antibodies designated 8g10/48 and 9e3/48 raised against mature asexual blood stages of plasmodium falciparum inhibit parasite growth in vitro. both antibodies bind to an epitope which includes the linear sequence ser thr asn ser and which is present in a cdna clone from a p. falciparum expression library. these antibodies recognise a glycosylated antigen of approximately 51 kda which is located on the merozoite surface membrane.	1988	2453800
epitopes recognized by human t cells map within the conserved part of the gp190 of p. falciparum.	in a study aimed at developing a vaccine against the asexual blood stages of plasmodium falciparum, two t cell epitopes were identified within a nonpolymorphic region of gp190 of plasmodium falciparum merozoites. the two epitopes, which were revealed by deletion analysis, stimulated human t cell clones. peptides containing sequences of the epitopes stimulated the cloned t cells and peripheral blood mononuclear cells (pbmc) from malaria-infected individuals. moreover, the t cell clones responded ...	1988	2453924
characterization of antibodies to sporozoites in plasmodium falciparum malaria and correlation with protection.	the antibody response to sporozoites of plasmodium falciparum and the role of these antibodies in protection against malaria have not been systematically investigated. an understanding of antisporozoite antibodies in natural infection is, however, important to the development of a human malaria vaccine. in a prospective study in thailand, an antibody response to sporozoites was observed only in individuals who developed parasitemia. antibodies were detected against an epitope in the repeat regio ...	1988	2454941
monoclonal antibodies to a synthetic peptide corresponding to a repeated sequence in the plasmodium falciparum antigen pf155.	mouse monoclonal antibodies were prepared against a synthetic peptide (eenvehda) corresponding to a tandemly repeated sequence in the c-terminus of the plasmodium falciparum antigen pf155. one antibody (igg1) producing hybridoma was studied in detail. the specificity of the antibody was determined by enzyme-linked immunosorbent assays using bovine serum albumin-conjugated or free peptides as solid phase antigens and various synthetic peptides for inhibition. the antibody reacted with pf155 as de ...	1988	2455227
malaria vaccines: immunogen selection and epitope mapping.	in recent years major efforts have been made to characterize parasite antigens thought to be suitable candidates for malaria vaccines. many of the relevant plasmodial antigens have been found to contain extensive areas of short amino acid sequences organized in tandem repeats. these are usually strongly antigenic, forming linear epitopes seen by antibodies of the infected host. several such epitopes have been identified and subunit vaccines are being designed in which synthetic peptides or gene ...	1988	2455387
features of t-cell recognition and antigen structure useful in the design of vaccines to elicit t-cell immunity.	in contrast to antibodies, t lymphocytes tend to recognize a limited number of immunodominant antigenic sites on a protein antigen. therefore, the effective design of synthetic or recombinant fragment vaccines would be better approached if these sites could be identified. from studies of the processing and genetically restricted presentation of the model protein antigen myoglobin to murine t cells, certain general principles have emerged which should be useful in this endeavour. the immunodomina ...	1988	2455388
characterization of antigen-expressing plasmodium falciparum cdna clones that are reactive with parasite inhibitory antibodies.	a plasmodium falciparum (fcr3 strain) lambda gt11 cdna expression library was constructed from trophozoite and schizont poly(a) rna and was screened immunologically with a pooled human immune serum from nigeria to form a gene bank of 288 positive clones. the gene bank was subsequently screened with parasite inhibitory mouse monoclonal antibodies (mmab) and with individual human liberian sera. two mmab, 43e5 and 5h10, strongly reacted with 8 and 3 cdna clones, respectively. several of those clone ...	1988	2456465
cytotoxic t cells specific for the circumsporozoite protein of plasmodium falciparum.	malaria is initiated by the inoculation of a susceptible host with sporozoites from an infected mosquito. the sporozoites enter hepatocytes and develop for a period as exoerythrocyte or hepatic stage parasites. vaccination with irradiated sporozoites can provide protective immunity and a recent study shows that this can also be conferred by immunization with a recombinant salmonella expressing only the circumsporozoite protein that normally covers the sporozoites. protection against infection is ...	1988	2456467
t-cell epitopes in pf155/resa, a major candidate for a plasmodium falciparum malaria vaccine.	immunogens included in a subunit vaccine should contain both b- and t-cell-activating sites to ensure anamnestic responses following reinfection after vaccination as well as antibody-independent cellular immunity. the plasmodium falciparum antigen pf155/resa, a major candidate for a vaccine against the asexual blood stages of this malaria parasite, was investigated for t-cell epitopes in its c-terminal amino acid repeat region, a region known to be conserved in different p. falciparum strains. i ...	1988	2456577
antigens with repeated amino acid sequences from the asexual blood stages of plasmodium falciparum.		1988	2457214
antigenic diversity in plasmodium falciparum.		1988	2457215
host responsiveness to malaria epitopes and immunopathology.		1988	2457218
characterization of a plasmodium falciparum polypeptide associated with membrane vesicles in the infected erythrocytes.	a plasmodium falciparum polypeptide (46 kda) associated with the infected erythrocytes of all asexual stages as well as immature gametocytes was identified by the monoclonal antibody (mab) 30b8.3. the expression of this protein was not dependent upon the knobby phenotype and was detected in parasites grown either in human or aotus erythrocytes. the antigen was heatstable, did not label with [14c]glucosamine, and was not sensitive to periodate oxidation. immunofluorescent staining patterns of mab ...	1988	2457806
mature liver stages of cloned plasmodium falciparum share epitopes with proteins from sporozoites and asexual blood stages.	the liver merozoites of malaria parasites are of paramount importance, as they initiate the parasite invasion of red blood cells and start the cycle associated with the clinical features of malaria. investigating liver merozoite antigen is difficult because of the lack of a rodent model of human malaria. in addition, only a low proportion of cells are obtained in vivo, the parasites from cebus and aotus monkeys are immature, and in-vitro experiments with liver cells are often confounded by conta ...	1988	2457864
reversal of chloroquine resistance in falciparum malaria independent of calcium channels.	racemic verapamil and close structural derivatives gallopamil and devapamil completely reverse chloroquine-resistance in falciparum malaria at 1-2 micromolar concentrations. if the r-(+) isomers of these calcium channel inhibitors are used, chloroquine-resistance is again completely reversed at similar doses. however, these r-(+) isomers do not bind to cardiovascular calcium channels which are stereospecific for the s-(-) isomer of the drugs. further since calcium channel inhibition is not invol ...	1988	2458107
naturally occurring antibodies to an epitope on plasmodium falciparum gametes detected by monoclonal antibody-based competitive enzyme-linked immunosorbent assay.	the antibody response to an epitope on gamete antigens of plasmodium falciparum in persons naturally exposed to malaria has been investigated by competitive enzyme-linked immunosorbent assay. the assay detects antibodies to an epitope on the 48/45-kilodalton (kda) gamete surface antigen by competition with horseradish peroxidase-labeled monoclonal antibody iic5-b10. five sera previously shown to immunoprecipitate the 230- and 48/45-kda antigens significantly inhibited iic5-b10 binding to an aver ...	1988	2459062
lack of cross-reactivity between variant t cell determinants from malaria circumsporozoite protein.	the discovery of polymorphism in the t cell determinants of the protein that covers the surface of malaria sporozoites, the circumsporozoite protein (csp), may have a negative effect on the course of development of a sporozoite-derived anti-malaria vaccine. comparison of csp gene sequences from plasmodium falciparum suggests, based on the lack of silent (i.e., synonymous) substitutions, that polymorphism is being biologically selected for in the field. thus, variation in t cell determinant seque ...	1988	2459211
sialic acid-dependent binding of plasmodium falciparum merozoite surface antigen, pf200, to human erythrocytes.	plasmodium falciparum merozoites, the extracellular stage of the erythrocytic cycle of the human malarial parasite, specifically invade human e. the major determinant of that specificity is the sialic acid residues of e glycophorin. in the present study we show that the merozoite surface ag, pf200 (m.w. 195,000 to 205,000), of two different isolates of p. falciparum, binds to the surface of human e but not e from other species not invaded by p. falciparum. pf200 does not bind to neuraminidase-tr ...	1988	2459245
identification of t epitopes within a potential plasmodium falciparum vaccine antigen. a study of human lymphocyte responses to repeat and nonrepeat regions of pf155/resa.	pbmc from melanesians who had high antibody reactivities to fusion proteins encompassing the 3' and the 5' repeat regions of the ring infected e surface antigen (pf155/resa), were tested for their ability to respond to synthetic and recombinant peptides representing regions of pf155/resa. the aim was to identify t cell epitopes within the ag. most of the synthetic peptides from the nonrepeat regions of pf155/resa were selected for study on the basis of their tendency to form amphipathic alpha-he ...	1988	2459246
extremely diverged actin proteins in plasmodium falciparum.	in a previous paper the nucleotide sequence of a complementary dna coding for a plasmodium falciparum actin protein (pf-actin i) has been described. here we present evidence that the genome of this human malaria parasite encodes for still another actin protein (pf-actin ii). via nucleotide sequence analysis of its coding dna we established the amino acid sequence of this protein. this sequence was compared with the pf-actin i sequence and those of a number of other actins. the comparative studie ...	1988	2459617
immunity to plasmodium sporozoites: recent advances and applications to field research.	the presence of antibodies against plasmodium falciparum sporozoites in humans living in malaria endemic areas was measured using as antigen the synthetic peptide (nanp)3, which represents the immunodominant region of the circumsporozoite (cs) protein. the results indicate that: i) the production of anti-cs antibodies is unrelated to the presence in the circulation of blood-stage parasites; ii) anti-cs antibodies, raised by natural inoculation, could exert a protective role against natural malar ...	1986	2459653
immune response of humans to the circumsporozoite protein of plasmodium falciparum: limited t cell response to the immunodominant central repeat region.	most adults in highly malarious areas have antibodies to the repeat region of the circumsporozoite protein of plasmodium falciparum. to determine if a t cell epitope on the repeat region stimulated t cell help for this antibody, we used r32tet32, a recombinant construct derived from the repeat region of the circumsporozoite protein of p. falciparum, to stimulate in vitro mononuclear cells from residents of an area hyperendemic for malaria. three groups differing in the length of time they had re ...	1988	2459979
prenatal immune priming in malaria: antigen-specific blastogenesis of cord blood lymphocytes from neonates born in a setting of holoendemic malaria.	the plasmodium falciparum-specific blastogenic response of cord blood lymphocytes (cbls) from neonates born in an area of holoendemic malaria of papua new guinea was compared to that of cbls from neonates born in hawaii, where malaria transmission does not occur. the average blastogenesis stimulation index of the new guinea cbls was 4.5 times greater than that of the hawaiian group of samples. eight of the 24 new guinea cbl samples had a stimulation index greater than ten and counts per minute r ...	1988	2460040
human t cells recognize polymorphic and non-polymorphic regions of the plasmodium falciparum circumsporozoite protein.	in order to characterize t cell epitopes in the plasmodium falciparum circumsporozoite (cs) protein sequence, we isolated t cell clones, from non-immune donors, which reacted with synthetic peptides corresponding to two predicted cs protein t cell epitopes. peptide cs.t3 (corresponding to a non-polymorphic region of the cs protein, residues 378-398) was recognized in association with either dr2 or drw9 restriction elements. t cell clones recognizing cs.t3 also reacted with the sporozoite-derived ...	1988	2461298
plasmodium falciparum: analysis of b epitopes of a polypeptide antigen expressed in escherichia coli, using monoclonal antibodies.	monoclonal antibodies were raised against a recombinant molecule corresponding to the polypeptide 72 kda, previously described as possibly related to protection in plasmodium falciparum infection. selection of hybridoma cell lines was done by immunofluorescence to guarantee the reactivity of the monoclonal antibodies both against the recombinant and the native molecule of the parasite. monoclonal antibodies were characterized by serological and immunochemical techniques. competitive binding assa ...	1988	2461317
[quantitative evaluation of parasitemia in tropical malaria].		1988	2462123
rapid diagnosis of malaria by acridine orange staining of centrifuged parasites.	a rapid diagnostic test for malaria based on acridine orange staining of centrifuged parasites in a microhaematocrit tube ('qbc' tube) was compared with the thick blood smear in 12 volunteers experimentally infected with plasmodium falciparum, 408 residents of a malaria endemic area, and 180 hospital patients with suspected malaria. in the experimentally infected volunteers, the qbc tube test and the thick blood smear were comparable and the qbc tube could detect as few as 4 parasites/microliter ...	1989	2462660
a malaria t-cell epitope recognized in association with most mouse and human mhc class ii molecules.	an ideal vaccine should elicit a long lasting immune response against the natural parasite, both at the t- and b-cell level. the immune response should occur in all individuals and be directed against determinants that do not vary in the natural parasite population. a major problem in designing synthetic peptide vaccines is that t cells generally recognize peptide antigens only in association with one or a few of the many variants of major histocompatibility complex (mhc) antigens. during the ch ...	1988	2462673
use and limitations of light microscopy for diagnosing malaria at the primary health care level.	recent developments in diagnostic techniques for malaria, particularly dna probes and sero-immunology, have raised questions as to how these techniques might be used to facilitate malaria diagnosis at the most peripheral levels of the primary health care system. at present, malaria diagnosis is based on the light microscope and is likely to remain so in the immediate future. this article describes how the diagnosis of malaria by light microscopy has been improved over the years, and expresses th ...	1988	2463112
bis(benzyl)polyamine analogs inhibit the growth of chloroquine-resistant human malaria parasites (plasmodium falciparum) in vitro and in combination with alpha-difluoromethylornithine cure murine malaria.	a number of bis(benzyl)polyamine analogs were found to be potent inhibitors of both chloroquine-resistant and chloroquine-sensitive strains of the human malaria parasite plasmodium falciparum in vitro (ic50 values = 0.2-14 microm). administration of one of the compounds, mdl 27695, which is n,n'-bis(3-[(phenylmethyl)amino]propyl)-1,7-diaminoheptane (c6h5ch2nh(ch2)3nh(ch2)7nh(ch2)3nhch2c6h5), at 10-15 mg/kg i.p. three times per day for 3 days in combination with 2% alpha-difluoromethylornithine ( ...	1989	2463635
a hybrid gene to express protein epitopes from both sporozoite and merozoite surface antigens of plasmodium falciparum.	the dna coding for parts of the repetitive amino acid sequence of plasmodium falciparum circumsporozoite protein has been spliced to a sequence encoding part of the precursor to the major merozoite surface antigens, to produce a hybrid gene. expression in escherichia coli produces a protein with antigenic determinants from both malaria proteins. antibodies raised against the expressed material react with both a peptide derived from the circumsporozoite repeat sequence, and the merozoite surface ...	1988	2464153
human lymphocyte proliferative response to a sporozoite t cell epitope correlates with resistance to falciparum malaria.	to identify vaccine relevant t cell epitopes on the circumsporozoite (cs) protein of plasmodium falciparum, the lymphocyte proliferative responses to 10 cs protein derived peptides were studied in 28 adult kenyans, and correlated with resistance to malaria. eight peptides, six of which were not overlapping, induced proliferation of lymphocytes from one to five volunteers, suggesting either genetic restriction of response to each of the t epitopes, or dominance of some t sites on the immunizing s ...	1989	2464643
activation of a plasmodium falciparum protease correlated with merozoite maturation and erythrocyte invasion.	protease-dependent processes of the p. falciparum schizogonic cycle are briefly described. the p. falciparum p76 protease is the first example of a biochemically regulated protease, the activation of which is related to merozoite maturation and/or erythrocyte invasion. the main known properties of the p76 protease are reviewed and some original results concerning its biosynthesis and biological properties are described.	1988	2465799
vaccine t-cell epitope selection by a peptide competition assay.	the binding of several peptides derived from the plasmodium falciparum circumsporozoite protein (cs protein) to the human major histocompatibility complex class ii proteins hla-dr5 and -drw6 was examined in a competition assay. fixed antigen-presenting cells (apcs) were incubated with various concentrations of each peptide and suboptimal concentrations of stimulator peptides. the binding of the cs peptides to dr5 or drw6 proteins was then determined in a proliferation assay using two established ...	1989	2466297
enhancement or inhibition of plasmodium falciparum erythrocyte reinvasion in vitro by antibodies to an asparagine rich protein.	a clone encoding a recombinant protein which reacted strongly with human antibodies from a donor clinically immune to malaria, was isolated from a genomic plasmodium falciparum library. mice injected with this protein, designated 10b, produced antibodies which reacted with all developmental stages of erythrocytic asexual parasites in indirect immunofluorescence. in immunoblotting, the same antibodies recognized two p. falciparum polypeptides of 36 kda and 33 kda. of three monoclonal antibodies r ...	1989	2467205
cross-reactive antigenic determinants present on different plasmodium falciparum blood-stage antigens.	a gene encoding a previously undescribed antigen of plasmodium falciparum has been isolated from a genomic expression library by use of a pool of human immune sera. northern blot analysis indicated that the gene is expressed at the late stages of the intra-erythrocytic cycle. this antigen, 332, contains a series of degenerated amino acid repeats. human antibodies affinity-purified on the 332 recombinant antigen reacted with a family of parasite proteins that are products of different genes. we i ...	1989	2467248
characterization of epitopes on the 25 kd protein of the macrogametes/zygotes of plasmodium falciparum.	a sexual stage-specific protein of plasmodium falciparum with a mr of 25,000 is one of the target antigens of transmission-blocking antibodies. the contributions of tertiary structure and post-translational modifications (glycosylation and acylation) to the structure of the epitopes on this protein were the subject of detailed investigations. after modification of the three-dimensional structure and modification or cleavage of carbohydrate groups and linked fatty acids, the immunological reactiv ...	1989	2467249
identification of a platelet membrane glycoprotein as a falciparum malaria sequestration receptor.	infections with the human malaria parasite plasmodium falciparum are characterized by sequestration of erythrocytes infected with mature forms of the parasite. sequestration of infected erythrocytes appears to be critical for survival of the parasite and to mediate immunopathological abnormalities in severe malaria. a leukocyte differentiation antigen (cd36) was previously suggested to have a role in sequestration of malaria-infected erythrocytes. cd36 was purified from platelets, where it is kn ...	1989	2467377
plasmodium falciparum: characterization of a 33-kda soluble antigen.	a 33-kda soluble antigen identified in the culture supernatant by patient serum and monoclonal antibodies was present in rings, trophozoites, schizonts, and merozoites of plasmodium falciparum. the antigen which is released into the culture supernatant by growing parasites was also observed in the host cells of trophozoites and schizonts and could be localized on the host cell surface. its specificity for the surface of trophozoites and schizonts was observed to decrease with increased duration ...	1989	2467824
a protective monoclonal antibody recognizes a variant-specific epitope in the precursor of the major merozoite surface antigen of the rodent malarial parasite plasmodium yoelii.	the precursor of the major merozoite surface ag (pmmsa) represents one of the principal molecules of the erythrocytic stages of malarial parasites. previously we reported that mab 302 recognizing the 230-kda pmmsa of plasmodium yoelii provided passive protection to mice challenged with this parasite. we now report that the protective capacity of mab 302 is variant specific, affording protection against infection with only three of five p. yoelii lines. immunoprecipitation analyses of their pmmsa ...	1989	2467942
comparison of the primary structure of the 25 kda ookinete surface antigens of plasmodium falciparum and plasmodium gallinaceum reveal six conserved regions.	the gene encoding the 25 kda ookinete surface antigen (pgs25) of plasmodium gallinaceum has been cloned using an oligonucleotide probe directed against one of the egf-like domains of the p. falciparum 25 kda ookinete surface antigen (pfs25). the pgs25 gene codes for a polypeptide of 215 amino acids, two amino residues less than pfs25. the deduced amino acid sequence contains a putative signal sequence at the amino-terminus, four tandemly repeated egf-like domains, and a hydrophobic region at the ...	1989	2468086
human and murine cd4 t cell epitopes map to the same region of the malaria circumsporozoite protein: limited immunogenicity of sporozoites and circumsporozoite protein.	the circumsporozoite (cs) protein is a candidate vaccine antigen for the sporozoite stage in the life cycle of the malaria parasite. using cs protein purified from recombinant baculovirus-infected cells and a panel of h-2 congenic mice, we are able to demonstrate that this protein is poorly immunogenic in terms of antibody production as a result of ir gene control. the immune response to the protein is also restricted following immunization with a cs-recombinant vaccinia virus or with sporozoite ...	1988	2468986
a versatile phage lambda expression vector system for cloning in escherichia coli.	by integrating fragments from the expression plasmids pjk2 and pjk4 into a derivative of the bacteriophage lambda, we constructed the phage expression vectors lambda jk2 and lambda jk4, which allow efficient cloning of genomic or cdna either into the 5' end or the 3' end of the lacz gene of escherichia coli. expression of barrier-free dna in phase may lead to fusion proteins consisting of active beta-galactosidase (beta gal) plus an additional polypeptide encoded by the inserted dna. analysis of ...	1989	2469628
human t cell recognition of polymorphic epitopes from malaria circumsporozoite protein.	lymphocytes obtained from forty individuals living in a malaria endemic area of west africa were tested for in vitro proliferative responses to peptides representing variant regions of the immunodominant t cell domain of the circumsporozoite protein (amino acids 326 to 345, referred to as th2r, and 361 to 380, referred to as th3r) from three distinct strains of plasmodium falciparum. a total of 83% of the individuals responded to at least one of the six peptides tested, confirming that these epi ...	1989	2469729
a protective monoclonal antibody recognizes a linear epitope in the precursor to the major merozoite antigens of plasmodium chabaudi adami.	the monoclonal antibody 5c10/66 was shown to afford strong protection in mice against fulminating plasmodium chabaudi adami infection. this was remarkable, as immunity to this organism is regarded to be mainly t-cell mediated. this antibody identified a 250-kda molecule in schizonts and an 83-kda fragment in merozoites. a cdna clone selected by 5c10/66 was the homologue of the plasmodium falciparum precursor to the major merozoite surface antigen (pmmsa). comparison with the p. falciparum sequen ...	1989	2471191
primary and secondary responses to (nanp) peptides by plasmodium falciparum sporozoites in various strains of mice.	the repetitive epitope (asn-ala-asn-pro = nanp) of the plasmodium falciparum circumsporozoite protein is considered as the basis for the development of a recombinant or synthetic subunit vaccine against malaria. vaccines consisting of (nanp)n molecules coupled to carrier proteins have already been tested in trials in human volunteers with partial success. in this paper we show that c57bl/6 mice, genetically responsive to carrier-free (nanp)n molecules, exhibit a secondary antibody response to (n ...	1989	2471257
peptide mapping of conformational epitopes in a human malarial parasite heat shock protein.	a protein of 75 kda is found in large quantities throughout the blood stages of the human malarial parasite, plasmodium falciparum. based on a partial amino acid sequence for p75, previously deduced from a cdna clone encoding approximately 40% of the molecule, secondary structural predictions were made. the potential role of long range effects on the tertiary structure of the protein stabilized by disulfide bridges was determined by reduction and alkylation of the fusion protein. five regions we ...	1989	2471738
nucleic acid analysis by sandwich hybridization.	one of the most significant achievements of the biochemist during the past two decades is the use to which immunologically based assays have been put in clinical diagnosis (hood et al.: immunology, 1984). the problem faced and surmounted by immunologists in effecting the transition from research tool to routine clinical assay bears a remarkable similarity to that confronting the molecular biologist today; i.e., how can nucleic acid hybridization, a technique of obvious potential (meinkoth and wa ...	1989	2471820
cell-mediated immune responses to vaccine peptides derived from the circumsporozoite protein of plasmodium falciparum.	t cell epitopes residing within vaccine candidate peptides have been identified by delayed-type hypersensitivity (dth) responses in mice. the recombinant sporozoite vaccine candidate, r32tet32, contains at least two t epitopes, one located within the repeat region and another in the tet tail. when c57bl/6 (h-2b) and balb/c (h-2d) mice were sensitized intradermally with r32tet32 or the truncated protein r32lr emulsified in cfa and challenged 5 days later with r32tet32, only h-2b mice recognized a ...	1989	2472448
cross-reacting antigens to pc96, a protective antigen of plasmodium chabaudi, in p. falciparum, p. vivax, and p. cynomolgi.	mice can be partially protected against plasmodium chabaudi by immunization with the antigen pc96, isolated from the erythrocyte membranes of infected mice. we used a pc96 specific monoclonal antibody to identify antigens which cross-react with pc96 in p. falciparum, p. vivax, and p. cynomologi. the cross-reactive molecules are antigens of mr 155,000 in p. falciparum, mr 220,000 in p. cynomologi. they are located in the surface membranes of infected erythrocytes. pc96 is characterized by immunoe ...	1989	2472747
immune response to a synthetic peptide corresponding to an epitope of a parasitophorous vacuole membrane antigen from plasmodium falciparum.	the parasitophorous vacuole membrane antigen qf 116 from plasmodium falciparum contains a defined epitope, dnnlvsgp, proximal to the carboxyl-terminus which binds to the inhibitory monoclonal antibody 8e7/55. a synthetic peptide containing this epitope was constructed and coupled to diphtheria toxoid as carrier. mice and rabbits were inoculated with this conjugate using cfa, saf-1, or aluminum phosphate as adjuvants. the peptide conjugate was highly immunogenic in both animal species, giving ris ...	1989	2473129
abnormal features of peripheral blood films from gambian children with malaria.	a series of peripheral blood films taken from gambian children with either acute or low-grade plasmodium falciparum infections were examined for abnormal features of the red and white cells. hypochromia and polychromasia with cytoplasmic stippling were predominant features in both groups. lymphocytosis, granulocytosis and plasmacytosis were common white cell abnormalities. an additional feature in films from patients with acute malaria was the presence of numerous atypical lymphocytes. a compari ...	1989	2473697