PubMed Health⌕ Search

Biomedical subjects

C Chougnet

Publications and source records attributed to C Chougnet.

At least 37 records · Page 2Linked to original sources
PubMed1995

Lack of correlation between HLA class II alleles and immune responses to Pf155/ring-infected erythrocyte surface antigen (RESA) from Plasmodium falciparum in Madagascar.

To investigate the relationships between predominant HLA class II alleles and immune responses to the Plasmodium falciparum ring-infected erythrocyte surface antigen (Pf155/RESA), 50 individuals from the highlands of Madagascar were followed-up from 1988 to 1991. The T cell reactivity and antibody responses to synthetic peptides (EENV)4, (EENVEHDA)4, and (DDEHVEEPTVA)3, representing major T and B epitopes of Pf155/RESA antigen, were assessed with an average of five determinations per individual over the four-year follow-up period. The T cell reactivity was investigated by lymphocyte proliferation and assays for interferon-gamma and interleukin-2 release. Antipeptide antibodies were measured using the Falcon assay screening test-enzyme-linked immunosorbent assay. The cumulative prevalence rates of cellular (range for the three peptides = 64-68%) and antibody responders (range = 70-74%) were similar for each peptide. The HLA class II typing was performed using polymerase chain reaction-restriction fragment length polymorphisms. The prevalent alleles or groups of alleles (frequency > 20%) were similar in responders and nonresponders, both for cellular and antibody responses to each peptide. These were HLA-DR 5 group and HLA-DQA1 *0601, *0101-0102-0104, HLA-DQB1 *0301, and HLA-DPB1 *0101-2601 alleles. Allelic distribution was similar in individuals presenting with (74%) or without (26%) a malaria attack during a 20-week follow-up conducted when malaria was hyperendemic (P > 0.05, by Fisher's exact test). Despite repeated immunologic measures that better identify the responders, no relationship was found between HLA class II alleles and the cellular or antibody responses to Pf155/RESA epitopes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Malaria and pregnancy in Cameroonian primigravidae: humoral and cellular immune responses to Plasmodium falciparum blood-stage antigens.

To investigate the mechanisms underlying the increased susceptibility to malaria in pregnant women, we determined the level of malaria-specific immunity in primigravidae. Humoral and cellular in vitro responses to unpurified (a crude schizont extract and a gametocyte preparation) and purified (affinity-purified Pf155/ring-infected erythrocyte surface antigen [RESA]) Plasmodium falciparum proteins, an immunodominant 45/47-kilodalton antigen from Mycobacterium bovis, and leucoagglutinin were compared between 52 primigravidae and 52 nonpregnant women from a semirural area of Cameroon. In vitro cellular responses were investigated in terms of lymphocyte proliferation, as well as production of interleukin-2 (IL-2), interferon-gamma (IFN-gamma), and IL-4. Cells from primigravidae exhibited a reduced proliferative response to schizont and gametocyte antigens, as well as to the M. bovis antigen. Conversely, the IL-2 response to Pf155/RESA was reduced. Interleukin-4 and IFN-gamma production did not appear to be affected in primigravidae. Antibody levels were also similar between pregnant and nonpregnant women. Our results underline the importance of examining several parameters of T cell activation with different types of antigens for a correct evaluation of the ability of lymphocytes to respond to malaria.

Adolescent↗
PubMed1994

Quantification of T cells reactive to Pf155/RESA peptides in Plasmodium falciparum-exposed individuals.

This study was designed to estimate, among T lymphocytes circulating in the peripheral blood of donors exposed to malaria parasites, the frequencies of those responding to Plasmodium falciparum antigens, and more specifically to Pf155/RESA peptides. The values of peptide-reactive T-cell frequencies were dispersed and rather low, ranging from 1:24,000 to undetectable (superior to 1:300,000). Subjects presented with different past exposure to parasites: either they had been repetitively exposed to malaria parasite infestation or they were recovering from a recent treated malaria attack. However, they had similar frequencies of T cells reactive to Pf155/RESA peptides. With cells from a minority of patients, "saw-tooth curves" were obtained, suggesting the existence of suppressor mechanisms operating in vitro in our limiting dilution assay.

Adult↗
PubMed1994

Antibodies to the 4-mer repeat of the ring-infected erythrocyte surface antigen (Pf155/RESA) protect against Plasmodium falciparum malaria.

To investigate the protective role of antibodies to the ring-infected erythrocyte surface antigen (Pf155/RESA) epitopes against Plasmodium falciparum clinical malaria, a cohort study was conducted in a Malagasy village over 7 months. In the 304 individuals included, 127 experienced P. falciparum attacks of under 1500 parasites/microliters with no clinical symptoms (protected individuals) and 177 experienced at least one clinical or preclinical P. falciparum attack requiring therapy (unprotected individuals). Antibodies to whole Pf155/RESA, to single epitopes of the 3' terminus, (EENV)4 and EENVEHDA(EENV)2 had higher responses in protected than in unprotected individuals (P = 0.006, P = 0.005, P = 0.05 respectively). Within the whole pattern of antibodies to the Pf155/RESA epitopes, only anti-R4 was related to protection independently of age and anti-wR. The Pf155/RESA 4-mer repeated epitope might be of interest for inclusion in a vaccine against the asexual blood stages of P. falciparum.

Adolescent↗
PubMed1993

Quantification of antibody-secreting lymphocytes that react with Pf155/RESA from Plasmodium falciparum: an ELISPOT assay for field studies.

We have adapted the enzyme-linked immunospot assay (ELISPOT) to enumerate the cells from Plasmodium falciparum-primed donors that produce IgG in vitro in response to malaria antigens. In vitro activation of cell cultures with two synthetic peptides (EENVEHDA)4, and (LGRSGGDIIKMQTL) corresponding to immunodominant T cell epitopes of the ring-infected erythrocyte surface antigen (Pf155/RESA) gave specific antibody-secreting cells (ASC) in five and six of the 15 P. falciparum-primed donors from Cameroon. Antibodies produced after a stimulation by synthetic peptides reacted also with total parasite proteins. However, crude P. falciparum antigen did not trigger a higher number of cells than did synthetic peptides. The absence of significant relation between the presence of sera antibodies and in vitro ASC against the same peptide suggests that the kinetics of circulating primed lymphocytes and antibodies are different. We evaluated 0.04-0.29% of peripheral blood B cells to be the frequency of memory cells specific to a single Pf155/RESA epitope in these donors. This study suggests that the ELISPOT assay should permit the analysis of B cell responses to malarial antigens at the single-cell level and its applicability to epidemiological field studies. This assay should be well suited to the identification of T helper epitopes capable of inducing the production of antibodies by human B cells, and will constitute an important tool for the selection of immunogens to be included in a subunit vaccine.

Adolescent↗
PubMed1993

Isotypic analysis of Plasmodium falciparum-specific antibodies and their relation to protection in Madagascar.

We previously reported that antibodies to the central repeat (DDEHVEEPTVA) of Pf155/RESA, a major Plasmodium falciparum antigen, were negatively related to antimalarial protection. We measured levels of isotype antibodies to this epitope and to P. falciparum in 76 Madagascan subjects. Immunoglobulin G (IgG) and isotype antibodies specific for P. falciparum had similar levels in individuals who were considered protected and those who were not (as determined during a longitudinal follow-up). The levels of IgG1 antibodies to (DDEHVEEPTVA)3 were higher in nonprotected subjects. The levels of total IgG and of other isotype antibodies had a similar tendency to be higher in nonprotected than in protected individuals.

Amino Acid Sequence↗
PubMed1993

Human immune responses to the Plasmodium falciparum ring-infected erythrocyte surface antigen (Pf155/RESA) after a decrease in malaria transmission in Madagascar.

A resurgence of falciparum malaria occurred in the central highlands of Madagascar in the 1980s and was responsible for an outbreak in 1986-1987. Since 1989, transmission has decreased dramatically. In April 1991, we investigated the humoral and cellular immune responses of 53 inhabitants of the village of Manarintsoa to six synthetic peptides that reproduced the major B and/or T cell epitopes of the Pfl 55/ring-infected erythrocyte surface antigen (RESA) of Plasmodium falciparum. The presence of RESA peptide-reactive T cells was assessed by lymphocyte proliferation assay as well as by detection of in vitro production of interferon-gamma and interleukin-2. The mean values of these cellular responses were low, and the results obtained in these three tests showed no correlation. Twenty-seven subjects presented with anti-RESA antibodies as detected by modified immunofluorescent assay, but the mean levels of anti-peptide antibodies were low. When compared with data obtained in January 1988 from the same subjects with three of the six peptides, the present data demonstrated a decrease in the response to these peptides in terms of both proliferative response and mean antibody titers. The mean values of anti-RESA antibodies remained unchanged. The fact that cellular and humoral responses to the major Pfl 55/RESA epitopes decreased but did not disappear probably reflects both the remainder of the acquired immunity resulting from the 1986-1987 malaria outbreak, and its conservation by the very low level of transmission since 1989.

Adolescent↗
PubMed1993

Humoral and cellular immune responses to the circumsporozoite protein of Plasmodium vivax in Madagascar.

Plasmodium vivax malaria is prevalent during the rainy season in the central highlands of Madagascar. In April 1991, we investigated the cellular and antibody immune responses of 53 inhabitants of Manarintsoa, a village in this area, to four antigens corresponding to B and T cell epitopes of the P. vivax circumsporozoite (CS) protein. Cellular responses were assessed by lymphocyte proliferation assay as well as by detection of interferon-gamma and interleukin-2 production in vitro. Cell culture was performed with two overlapping synthetic peptides (CSVTCGVGVRVRSRVNA [amino acids 311-326]) and VRVRSRVNAANKKPED [amino acids 319-334]) from the vicinity of the highly conserved region II of the CS protein. In at least one of the three assays, cells from seven subjects showed a positive response to CSVTCGVGVRVRSRVNA, while cells form 14 subjects responded to VRVRSRVNAANKKPED. Antibodies directed against the two recombinant antigens, NS1(81)V20 and rPvCS-2, both of which contain the entire central repeat region of the P. vivax CS protein, plus regions I and II in the case of rPvCS-2, were measured by the Falcon assay screening test-enzyme-linked immunosorbent assay. Eight and nine subjects had antibodies to NS1(81)V20 and rPvCS-2, respectively. The presence of antibody responses to both recombinant antigens was related (P = 0.02, by Fisher's exact test), but was not related to the presence of a cellular response to peptides from vicinity of region II (P > 0.1, by Fisher's exact test).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Is immunity to malaria really short-lived?

Protection against Plasmodium falciparum malaria is usually considered to be the cumulative product of repeated exposure to parasites, and thus a function of age, in endemic areas. The recent outbreak of malaria in the central highlands of Madagascar gave Philippe Deloron and Claire Chougnet the opportunity to compare the incidence of malaria in children and young adults exposed to malaria for the first time, with that in older adults who spent their childhood in the study area before malaria control was introduced. Protection, as well as immune responses to two major P. falciparum antigens, was not related to age. Individuals older than 40 years were more protected than were younger adults. This increased protection was probably due to immunological memory.

Journal Article↗
PubMed1992

Kinetics of lymphocyte subsets from peripheral blood during a Plasmodium falciparum malaria attack.

Variations of lymphocyte subsets were followed longitudinally in 16 patients during an acute falciparum malaria attack. Before treatment, lymphocyte numbers were highly reduced, but the subset distribution was similar to that of healthy individuals. After parasite clearance, lymphocyte counts were normalized and the subset distribution was unchanged. This led to a normalization of all the absolute counts of lymphocyte subsets, except CD8+. The fast normalization of lymphocyte counts suggests that the initial decrease in lymphocyte numbers may reflect sequestration. Magnitude and kinetics of this variation were not related to parasite density or to severity of the attack. Activated T cells (CD3+HLA-DR+) were fewer in African than in European patients, suggesting the importance of the past exposure to malaria parasites in reallocation phenomena. These variations in lymphocyte numbers must be taken into account in the design and the analysis of cellular investigations in patients experiencing a falciparum malaria attack.

Adult↗
PubMed1991

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 from its nonrepeated amino-terminal region, gave rise to significant IgG secretion. Supernatants from lymphocyte cultures activated with either one of these peptides contained antibodies reacting with P. falciparum Ag in immunofluorescence assays and with Pf155/RESA peptides in a slot blot assay. No anti-P. falciparum antibodies were induced in the medium controls by lymphocyte stimulation with either tetanus toxoid or PWM. Induction in vitro of anti-Pf155/RESA antibodies was correlated with the presence of such antibodies in the sera of the lymphocyte donors, suggesting that the induction of antibody secretion reflected a secondary response in vitro of in vivo primed cells. Inspection of antibody profiles in individual donors revealed that the peptide corresponding to a sequence in the 3' repeat region induced anti-Pf155/RESA peptide antibodies reacting with identical or related and cross-reacting sequences in the 3' or 5' repeat region of the molecule. In contrast, the peptide corresponding to a nonrepeated T cell epitope in the amino terminus of the molecule only induced antibodies to an immunodominant amino-terminal B cell epitope partly overlapping with the T cell reactive sequence. Similar findings were made in the lymphocyte donors' plasma, frequently displaying significant correlations between antibody reactivities to the repeat peptides but not between these reactivities and those to the amino-terminal peptide. The marked specificity of this antibody formation in vitro suggests an underlying process of cognate recognition involving Ag-specific T and B cells reacting with different segments of the inducer peptide. The present experimental system should be well suited for identification of Th epitopes capable of inducing the production of antibodies of defined specificity in the human system.

Adolescent↗
PubMed1991

Assessment of the protective value of antibodies to the Plasmodium falciparum ring-infected erythrocyte surface antigen (RESA): an epidemiologic study in Madagascar.

The ring-infected erythrocyte surface antigen (RESA), a Plasmodium falciparum merozoite antigen, is a major vaccine candidate against falciparum malaria. To investigate the protective role of antibodies to RESA and its 4-mer, 8-mer, and 11-mer repeated amino acid sequences under conditions of natural exposure, a case-control and a cohort study were carried out in 1988 in a rural community in Madagascar where malaria reappeared recently. Fifty cases with greater than 1,000 P. falciparum per microliter of blood, and 45 controls with a negative blood smear were enrolled and sera were collected. Forty-one controls were followed for 20 weeks to identify malarial attacks. Protection against clinical malaria was assessed by the absence of malarial attacks requiring therapy. At enrollment, positivity rates and reactivity levels to RESA or repeats were similar in cases and controls. The 11-mer repeat antibody level was higher in the 26 controls who experienced at least one malarial attack during follow-up than in the 15 other controls (p less than 0.01). Thus, antibodies to the 11-mer repeat were predictors of the subsequent appearance of the disease. After adjustment for antibodies to the 11-mer repeat, antibodies to whole RESA had a negative predictive value on the occurrence of malarial attacks (p = 0.04). Different epitopes within the RESA molecule may elicit production of antibodies with different activities.

Adult↗
PubMed1991

Transmission and epidemiology of newly transmitted falciparum malaria in the central highland plateaux of Madagascar.

The recent reappearance of Plasmodium falciparum in the central highland plateaux of Madagascar has led to an important increase in both morbidity and mortality in the population. To understand the phenomena that originated this outbreak, and to evaluate the clinical and biological reactions of the population, we conducted entomological surveys during the whole malaria transmission season of 1988. In parallel, 41 individuals presenting with a malaria attack in January were given a curative antimalarial treatment and were followed weekly for 20 weeks, until the end of the transmission season, in June. During the follow-up, individuals presenting with a clinical malaria attack or with a parasite density above 5000 per mm3 of blood were again given antimalarial treatment. Overall, individuals presented with an average of 5.6 thick blood smears positive for P. falciparum, and 1.4 malaria attacks requiring treatment. Plasmodium falciparum prevalence rates gradually increased to 53.8% in April, one to two months after the observed peak of transmission, then decreased to 15.4% at the end of follow-up. The proportion of P. falciparum infections with clinical symptoms did not follow a similar temporal evolution and was significantly lower than at enrollment. Splenic rates gradually decreased from 29.3-2.6%, while anti-P. falciparum and anti-Pfl55/RESA antibodies increased. For the whole transmission season individuals experienced a mean 1.5 infective bites; the malaria vectors were Anopheles gambiae s. 1 and An. funestus. This study demonstrates that, in this population newly exposed to P. falciparum infections, almost all sporozoite inoculations lead to blood parasite infection requiring treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

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 Pfl55/RESA capable of inducing lymphocyte proliferation. Cellular response to all studied peptides was more frequently observed in individuals living in France for less than one year than in individuals living in France for a longer time. T-cell proliferation in the presence of the tetrapeptide and of the octapeptide from the C-terminus repeat of Pfl55/RESA was related, with an immunodominance of the tetrapeptide over the octapeptide. Cellular responses to the CS protein repeat and to the 11-amino-acid peptide from the Pfl55/RESA N-terminus were the longest lasting after termination of exposure. In a given individual, cellular and humoral responses were not related for any peptide studied.

Adolescent↗
PubMed1991

Protective value of elevated levels of gamma interferon in serum against exoerythrocytic stages of Plasmodium falciparum.

In vitro experiments suggested that gamma interferon, CD8+ T cells, and anticircumsporozoite antibodies inhibited the exoerythrocytic stages of malaria parasites. To assess the role played in vivo by these factors, we conducted a prospective study in Madagascar. Forty individuals with a negative blood smear were followed for 8 weeks to detect the appearance of parasites in blood. Nineteen subjects remained negative for malaria, whereas 21 individuals became positive during follow-up. Among these, seven presented with blood parasites within the first 2 weeks and were excluded, as they probably were infected by sporozoites at enrollment. When measured at enrollment, antibodies to the synthetic peptide (NANP)5, lymphocyte proliferation with (NANP)5, and various lymphocytes subsets were similar among individuals that later presented with a Plasmodium falciparum blood infection or were not infected. Conversely, the level of gamma interferon in serum was higher in individuals that did not present with a P. falciparum infection during follow-up. These data suggest that gamma interferon may inhibit the malaria exoerythrocytic stages of development under in vivo conditions, as it does in vitro.

Adolescent↗
PubMed1991

Lymphoproliferative responses to synthetic peptides from merozoite ring-infected erythrocyte surface antigen and circumsporozoite protein: a longitudinal study during a falciparum malaria episode.

Proliferative responses of peripheral blood lymphocytes to synthetic peptides representing major epitopes of two malaria antigens (the merozoite ring-infected erythrocyte surface antigen and the sporozoite circumsporozoite protein) were investigated in Madagascar during a clinical Plasmodium falciparum episode. Thirty-seven patients greater than 10 years of age were enrolled at the beginning of the malaria transmission season and followed for four weeks. At enrollment, when the subjects presented with an acute infection, lymphocytes recovered from approximately 30% of them proliferated after peptide stimulation. These proliferative responses decreased sharply one and two weeks after treatment, with less than 10% responding to each peptide. Four weeks after treatment, the responses were only partially restored. The amplitude of these variations was not related to the initial parasitemia. At the individual level, proliferative response to each peptide varied greatly during the followup period, and this variation was unrelated to the presence of parasites in the blood.

Adolescent↗
PubMed1990

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 a specific antigen was addressed.

Adolescent↗