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T Fandeur

Publications and source records attributed to T Fandeur.

At least 37 records · Page 2Linked to original sources
PubMed1993

The virulent Saimiri-adapted Palo Alto strain of Plasmodium falciparum does not express the ring-infected erythrocyte surface antigen.

The Palo Alto strain of Plasmodium falciparum is highly virulent for the Saimiri sciureus monkey. We have observed that these parasites do not express the Ring-infected erythrocyte surface antigene (RESA) gene. Immunoblots indicated that the Pf155/RESA protein was absent. The RESA mRNA could not be detected. Polymerase chain reaction and Southern blot analysis demonstrated that this lack of expression is due to gene rearrangements. The majority of the Palo Alto parasites have a deletion of the entire RESA gene, whereas in a minor fraction the RESA sequences remain detectable, but the 5' miniexon 1 is inverted. These data show that the RESA protein is dispensable for in vivo parasite growth, at least in Saimiri monkeys.

Adaptation, Physiological↗
PubMed1993

The RESA-2 gene of Plasmodium falciparum is transcribed in several independent isolates.

The relevance of the ring-infected erythrocyte surface antigen (RESA) of Plasmodium falciparum as a malaria vaccine candidate has been questioned of late because RESA-deficient parasites have been found to multiply normally in culture or in monkeys. The RESA-2 gene was recently described as a pseudogene highly homologous to RESA. In this report, we demonstrate that RESA-2 is not a pseudogene, because we were able to detect RESA-2 transcripts in asexual blood stages of multiple isolates by using polymerase chain reaction on reverse-transcribed mRNA. Transcription of RESA-2 was observed whether or not the isolates studied expressed the RESA protein.

Amino Acid Sequence↗
PubMed1992

Protection of squirrel monkeys against virulent Plasmodium falciparum infections by use of attenuated parasites.

We previously showed that the Uganda Palo Alto line of Plasmodium falciparum propagated in Saimiri monkeys and the line maintained in culture in human erythrocytes for many years in our laboratory are genetically unrelated (T. Fandeur, S. Bonnefoy, and O. Mercereau-Puijalon, Mol. Biochem. Parasitol. 47:167, 1991). When injected into a splenectomized Saimiri monkey, the in vitro-derived Palo Alto population procured a long-lasting, low-grade parasitemia that was spontaneously resolved by the animal. This line was propagated by serial blood transfers in two other monkeys without enhancement of the virulence of the parasites. The genetic characteristics of parasite samples corresponding to the different passages of the line in monkeys were stable for the several markers examined (pPF11.1, MSA1, and MSA2), although microheterogeneity was detected in telomeric and subtelomeric regions of chromosomes. Interestingly, in vitro-derived Palo Alto parasites induced a strong, potent immunity that enabled the monkeys to completely block subsequent challenge with two different heterologous lethal P. falciparum lines. These attenuated parasites are thus genetically stable in monkeys and represent an attractive model for assessing the feasibility of a live attenuated malaria vaccine.

Animals↗
PubMed1991

A study of the genomic diversity of Plasmodium falciparum in Senegal. 2. Typing by the use of the polymerase chain reaction.

The genomic polymorphism of Plasmodium falciparum was investigated in a series of samples collected in Senegal during one transmission season. PCR analysis was performed on several genes coding for blood-stage antigens: the gene for the major merozoite surface antigen P190, the gene for the second merozoite surface antigen MSA2 and the gene coding for antigen 96tR/GBP130. In each case, several distinct forms of the genes studied were observed. Both the MAD20 and K1 allelic families of P190 genes were observed. PCR analysis of a single variable region did not differentiate each isolate. However, when the data obtained for several markers are combined, each isolate had a specific genotype. Thus, using PCR to study in parallel several loci is a useful tool to genetically type strains.

Alleles↗
PubMed1991

Plasmodium falciparum: genetic stability of the Uganda Palo Alto strain propagated in the squirrel monkey (Saimiri sciureus).

The Uganda Palo Alto strain of Plasmodium falciparum has been extensively used in several laboratories to infect Saimiri monkeys. In the study reported here three distinct lines derived by parallel serial blood transfers from a single 10-year-old passage of the Palo Alto strain were examined for genetic diversity using the polymerase chain reaction and restriction mapping techniques. A comparison of the PF 11.1, P190, MSA2, S-Ag, and KAHRP genes indicates that these parasite lines are apparently homogeneous and stable. Nevertheless, microheterogeneity was observed with molecular probes which are known to easily detect restriction fragment length polymorphisms (rep 20 and telomeric probes). These data show that the genetic characters of the strain can be considered monomorphic and are conserved after multiple passages in the squirrel monkey.

Animals↗
PubMed1991

In vivo and in vitro derived Palo Alto lines of Plasmodium falciparum are genetically unrelated.

The Uganda Palo Alto strain of Plasmodium falciparum (FUP) is routinely used as a reference isolate in a number of laboratories. It is one of the few P. falciparum strains that can both be propagated in vivo in monkeys and maintained in culture. The Palo Alto parasites have been characterized for several biochemical and molecular markers, but many of the data reported so far are contradictory. We have analyzed and compared by Southern blotting, PCR and DNA sequencing, several DNA preparations obtained from different FUP lines and from the FCR3 strain. We show here that FUP lines propagated in Saimiri monkeys (FUP/S) and those maintained in culture (FUP/C) for many years in our laboratory differ in the various genetic markers investigated (P190, MSA2, S-Ag, KAHRP, 96 tR, pPFPA rep 20 and pPF 11.1). Therefore, at the present, two genetically unrelated strains of P. falciparum widely distributed over numerous laboratories are designated FUP/Palo Alto. When the Saimiri-propagated FUP/S line was used to initiate an in vitro culture in human red blood cells, no evidence of instability or genetic drift was obtained. The growth rate and genomic characteristics remained constant for several months. Likewise, the FUP/C line was found unchanged after three transfers in Saimiri monkeys. FUP/CP parasites were shown to be genetically closely related to FCR3. In addition, a subline of FUP/C strain selected by repeated flotation on gelatin was found to differ in several characters such as KHARP, P190 and S-antigen genes, which are known to be located on different chromosomes.

Amino Acid Sequence↗
PubMed1989

A two-site sandwich immunoradiometric assay of squirrel monkey (Saimiri sciureus) IgM using monoclonal antibodies.

Nine hybrid clones secreting antibodies to squirrel monkey (Saimiri sciureus) IgM were produced and two of these (1F1G5 and 5H11B3) were selected for further studies. These non-precipitating monoclonal antibodies reacted with two distinct repetitive antigenic determinants, probably of the conformational type, only present on the native or SDS-denatured IgM molecule. Reduction of the pentamer with 2-mercaptoethanol led to complete destruction of the corresponding epitopes. 1F1G5 antibodies from ascitic fluids were used in the purification of monkey IgM by affinity chromatography. The characteristics of 1F1G5 and 5H11B3 MAbs permitted the development of a solid-phase two-site immunoradiometric assay for the measurement of IgM levels in serum specimens taken from healthy animal donors of both sexes.

Animals↗
PubMed1988

Long-term protection of squirrel monkeys (Saimiri sciureus) against Plasmodium falciparum challenge inoculations after various time intervals.

When used as an experimental host for Plasmodium falciparum, the squirrel monkey Saimiri sciureus, intact or splenectomized, develops a significant, long-lasting, protective immunity against the blood stages of this parasite. In the present study, this length of protection after a single initial infection was determined by test infections carried out at varying intervals of time in 26 splenectomized animals. An initial period of about 7 months was observed, which was characterized by a marked resistance to trial reinfestations by a homologous as well as a heterologous strain. A second period was observed during which the primates became sensitive to the parasite in varying degrees. These observations single out the squirrel monkey in comparison with other experimental hosts tested under similar conditions and underline the value of research on antimalarial vaccinations, because when confronted with parasite antigens, the organism can produce the immunological response necessary to control a test infection.

Animals↗
PubMed1987

Characterization of a 96-kilodalton thermostable polypeptide antigen of Plasmodium falciparum related to protective immunity in the squirrel monkey.

Protective immunity against Plasmodium falciparum malaria in the squirrel monkey (Saimiri sciureus) is, in part, antibody mediated. We have previously shown that polypeptides of 41, 76, and 96 kilodaltons (kDa) are specifically immunoprecipitated with monkey sera which are protective in passive transfer experiments. We report here that three different 96-kDa polypeptides, of pI 5.15, 5.25, and 5.35, can be visualized when parasite extracts are analyzed in bidimensional gels. Only one of them (of pI 5.25) was stable after being heated at 100 degrees C for 5 min. The 96-kDa thermostable polypeptide of pI 5.25 was immunoprecipitated by protective monkey sera and by sera from adult humans living in hyperendemic areas and thus seems to be correlated with humoral protective immunity. This antigen was found in culture supernatants at the time of schizont rupture. It was synthesized during the schizont stage and is apparently not a glycoprotein.

Adult↗
PubMed1986

[ELISA test in sero-epidemiologic studies of human malaria. Evaluation of an antigen prepared from erythrocytes of Saimiri sciureus experimentally infected with Plasmodium falciparum].

A soluble antigen was prepared from squirrel monkeys (Saimiri sciureus) infected with blood-passaged Plasmodium falciparum, and evaluated in an enzyme-linked immunosorbent assay (ELISA) as a potent antigen for malaria diagnostic. The specificity, reproducibility and sensibility of the test showed the suitability of our antigenic preparation in detecting antibodies, IgG and IgM, in patients with P. falciparum infections. Thus, the Saimiri monkey represents an interesting alternative to the classicals sources of parasites from which P. falciparum antigens are commonly extracted (continuous culture and natural infections).

Animals↗
PubMed1984

Protective immunization of the squirrel monkey against asexual blood stages of Plasmodium falciparum by use of parasite protein fractions.

We had previously shown that two polypeptides of Plasmodium falciparum are preferentially recognized by antibodies of resistant squirrel monkeys Saimiri sciureus. Free parasites were isolated from synchronized cultures on human erythrocytes initially inoculated with infected Saimiri erythrocytes. Crude extracts were prepared from mature schizont stages and electrophoresed on preparative NaDodSO4/polyacrylamide gels. Two groups of five monkeys were immunized with protein fractions eluted from the 75- and 100-kilodalton regions of the gels. Strong protection against challenge by the homologous strain of P. falciparum was induced in both groups. Analysis of specific anti-malarial antibodies revealed a homogeneous response of all the animals against a few polypeptides of the mature parasite.

Animals↗
PubMed1984

In vitro and in vivo studies on protective and inhibitory antibodies against Plasmodium falciparum in the Saimiri monkey.

Immunoglobulins (Ig) were purified from serum or ascitic fluids of Saimiri monkeys infected with Plasmodium falciparum and with differing levels of functional immunity. Their protective activity was assessed in studies of passive transfer of immunity in vivo, and their neutralizing activity was measured in studies of parasite inhibition in vitro in cultures of human or Saimiri RBC. Although protective and inhibitory antibodies were detected in different Ig preparations, the levels of these activities were not directly correlated. Some Ig preparations, showing high protective activity, provide little or no inhibition of the parasite in vitro. Conversely, inhibitory activity was present in Ig preparations unable to confer protection in vivo. These results indicate that protective antibodies are active through a more complex immune mechanism than simple neutralization probably involving cellular immunity.

Animals↗
PubMed1984

Immunization against Plasmodium falciparum asexual blood stages using soluble antigens.

Saimiri sciureus monkeys have been successfully immunized against a human malaria parasite, Plasmodium falciparum, using soluble antigens purified from schizont and merozoite extracts. High levels of antibodies reacting with schizont and merozoite specific polypeptides of 140 and 200 kdaltons were detected in the sera of protected monkeys. The five immunized monkeys survived a challenge infection with 5 X 10(7) parasites inducing a fulminant disease in control monkeys.

Animals↗
PubMed1983

Saimiri sciureus (karyotype 14-7): an alternative experimental model of Plasmodium falciparum infection.

In an earlier manuscript, we described the first phase of adaptation of the Palo Alto I strain of Plasmodium falciparum to Saimiri sciureus (squirrel monkeys). Now, after more than 50 P. falciparum blood transfers in splenectomized Saimiri, the parasite has become fully adapted to this experimental host. A highly reproducible pattern of infection is evident in these splenectomized animals, which is characterized by a rapidly rising parasitemia and a lethal outcome. In intact animals, the course of infection is extremely variable, with a tendency towards high parasitemias and low survival rates. After 60 passages, the parasites have maintained their invasiveness for human red blood cells and can easily be propagated by continuous in vitro culture. Conversely, prolonged in vitro culture of this parasite strain has not decreased its infectivity for Saimiri. Intact, P. falciparum-infected animals rapidly develop a high degree of resistance to reinfection, even when treatment is initiated shortly after detection of the first circulating parasites. Under identical conditions, splenectomized animals develop a variable degree of protection. The potential usefulness of squirrel monkeys as experimental hosts of P. falciparum and P. vivax malaria is discussed in light of the present findings.

Animals↗
PubMed1981

Ascites production in the squirrel monkey (Saimiri sciureus).

A method is described for inducing the production of large amounts of ascitic fluid (AF) in the squirrel monkey Saimiri sciureus. The total amount of protein in the induced AF is close to 60% of that in the serum. Electrophoretic analysis of serum and AF samples from the same monkey revealed similar protein patterns, including gamma globulins. Antibody titers against Plasmodium falciparum in infected monkeys, measured by indirect immunofluorescence, were also comparable in serum and AF.

Animals↗
PubMedDate not supplied

Structure and function of a thymic peptide is mimicked by Plasmodium falciparum peptides.

Numerous Plasmodium falciparum antigens contain repetitive amino acid sequences. Two blood stage antigens, Pf11-1 and Pf332, were characterized in our laboratories and present high cross-reactivities, defining a family of cross-reacting antigens. In this report, we show that amino acid sequence homologies might explain these cross-reactivities, but that they extend to polypeptides from the host, namely thymosin-alpha 1 (T alpha 1). An antiserum raised in chickens and Saimiri monkeys against the synthetic Pf11-1 peptide cross-reacts with synthetic T alpha 1. Synthetic Pf11-1 and Pf332 peptides share some of the biological activities of T alpha 1. These results are discussed with respect to the mechanisms devised by malaria parasites for escape from the host immune response.

Amino Acid Sequence↗