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Biomedical subjects

G Riveau

Publications and source records attributed to G Riveau.

At least 19 recordsLinked to original sources
PubMed2001

Features of the antibody response attributable to plasmid backbone adjuvanticity after DNA immunization.

DNA vaccination induces antigen-specific immune responses with characteristics distinct from other vaccination modes. In the present study, the contribution of the plasmid backbone adjuvant effect to the quality of the DNA-raised antibody response was investigated. For this purpose, three intradermal primings were compared in mice using: (1) the recombinant Schistosoma haematobium glutathione S-transferase antigen (rSh28GST): (2) rSh28GST supplemented with a non-coding plasmid; and (3) a Sh28GST-encoding plasmid. In contrast to immunization with the protein, DNA immunization elicited a very stable antibody (Ab) response over a prolonged period of time. This feature was attributed to the plasmid backbone, because co-administration of the non-coding plasmid with rSh28GST allowed the maintenance of the specific Ab response. A strong anamnestic Ab response was induced after intradermal boost with rSh28GST only in the mice primed with pMSh. This indicated that the selective ability of DNA vaccination to induce memory humoral response was independent of the plasmid backbone. In contrast the plasmid backbone was found to strongly participate in the preferential IgG2a Ab production observed. These results suggest that, following DNA immunization, the Th1-biased profile and the maintenance of the long-lived Ab response could be attributed to an adjuvant effect of the plasmid backbone during priming, whereas the strength of B-cell memory was independent of this effect.

Adjuvants, Immunologic↗
PubMed2001

Medullary gnathostomiasis in a white patient: use of immunodiagnosis and magnetic resonance imaging.

A 48-year-old French diplomat presented with a sensory-motor paraparesis of rapid onset, leading to paraplegia. Successive magnetic resonance image scans showed lesions of the thoracic spinal cord that were at different levels from one examination to the next. Specific anti-gnathostome antibodies were detected by means of enzyme-linked immunosorbent assay and Western blot test in both plasma and cerebrospinal fluid. Albendazole treatment prevented disease progression, but only partial regression of the neurologic symptoms was obtained.

Albendazole↗
PubMed2001

Immunostimulatory effect of IL-18-encoding plasmid in DNA vaccination against murine Schistosoma mansoni infection.

In vivo delivery of DNA encoding antigens is a simple tool to induce immune responses against pathogens. This approach to vaccination also offers the possibility to codeliver plasmids encoding immunomodulatory molecules in order to drive immune responses towards optimal protective effects. In the murine model of Schistosoma mansoni infection, vaccination inducing a Th1 profile has been shown to be protective. In this study, we used a plasmid encoding the Th1-promoting cytokine IL-18, since we observed that percutaneous infection of Balb/c mice strongly induced the production of IL-18 mRNA in the skin. Intradermal injection of the IL-18-encoding plasmid prior to infection did not interfere with parasite migration through the skin although it led to a local and transient cellular infiltration. When the IL-18-encoding plasmid was codelivered with a S. mansoni glutathione S-transferase (Sm28GST)-encoding plasmid, a 30-fold increase of antigen-specific IFN-gamma secretion by spleen cells was observed in comparison to spleen cells from mice that had received only the Sm28GST-encoding plasmid. This immunostimulatory effect was related to a significant protective effect (28% reduction in egg laying and 23% reduction in worm burden) which was attributed to a cooperative effect between both plasmids. Therefore, this study shows that codelivery of an IL-18-encoding plasmid with an antigen-encoding plasmid can stimulate specific cellular responses and induce protective effects against S. mansoni infection.

Animals↗
PubMed2001

Gender-dependent specific immune response during chronic human Schistosomiasis haematobia.

The cellular and humoral acquired immune responses to Schistosoma haematobium 28 kD gluthathione S-Transferase (Sh28GST) antigen were evaluated in a Senegalese population chronically infected with S. haematobium parasite. We show a gender-dependent immune response in adult individuals presenting similar intensities of infection. Indeed, the specific IgA response and production of TGF-beta and IL-10 were found significantly higher in females compared to males. In addition, we showed that this profile was combined with a weak production of Th1-related cytokines (TNFalpha and IFNgamma) and was associated with an absence of proliferation to the antigen. A significantly higher Nuclear Matrix Protein 41/7 secretion, an apoptosis marker, was specifically observed in mononuclear blood cell cultures of females suggesting that a specific cell death process was engaged in a gender-dependent manner. This specific profile could be associated with the so-called T helper type-3 (Th3) immune response specifically promoting the production of IgA and would be developed upon the down-regulation of the specific Type-1 response by a probable cell death mechanism. This gender-dependent immune regulation, which may be under the influence of nonimmunological factors like sexual hormones, may be related to the chronicity of the infection.

Adult↗
PubMed2000

Interleukin-18 modulates immune responses induced by HIV-1 Nef DNA prime/protein boost vaccine.

Many different HIV-1 vaccine strategies have been developed, but as yet none has been completely successful. Promising results from combined DNA prime/protein boost vaccines have been reported. Specific immune responses generated by DNA vaccines can be modulated by the co-delivery of genes coding for cytokines. In this study, we have used the intradermal route by needle injection of a plasmid coding for the HIV-1 Nef accessory protein. We show that DNA prime/protein boost vaccine combinations increase the humoral and cellular immune responses against HIV-1 Nef and that the co-injection of DNA encoding Interleukin-18 (IL-18) modulates the specific immune response towards a Th1 type.

AIDS Vaccines↗
PubMed2000

Sex-dependent neutralizing humoral response to Schistosoma mansoni 28GST antigen in infected human populations.

The reduction of Schistosoma fecundity observed after experimental vaccination with the Schistosoma mansoni 28-kDa glutathione S-transferase (Sm28GST) antigen has been related to the inhibition of glutathione S-transferase (GST) enzymatic activity by specific antibody. The humoral immune response to the protective antigen Sm28GST and to the epitopes involved in the enzymatic site (amino acid ¿aa sequences 10-43 and 190-211) was evaluated in infected individuals before chemotherapy treatment. The capacity of the serum samples to inhibit GST enzymatic activity was assessed. Specific IgG3 response was predominant in the male population with a low intensity of infection and was associated with maximal GST inhibition. In contrast, the neutralizing activity of serum samples from women with a low intensity of infection was correlated with high specific IgA response specifically directed toward the 190-211 epitope. These results strongly support the hypothesis that GST-neutralizing IgG3 and IgA isotypes are sex dependent. The relationship of this specific acquired immune response with the level of intensity of infection is discussed.

Adolescent↗
PubMed2000

Vaccine properties of antigens entrapped in microparticles produced by spray-drying technique and using various polyester polymers.

The present study investigated the suitability of various microparticles produced by spray-drying technique to entrap and preserve the physiochemical and biological properties of an antigen. These microparticles were constituted either by poly(lactide) polymers characterized by various molecular weight or poly(lactide-co-glycolide) polymers. The recombinant 28 kDa glutathione S-transferase of Schistosoma mansoni (rSm28GST) characterized by major epitopes involved in the active site of this enzyme was selected as model antigen. The microparticles were characterized by a mean size </=5 microm and an antigen loading of approximately 2% (w/w). The analysis by SDS-PAGE electrophoresis of the rSm28GST released from microparticles confirmed the conservation of its physicochemical characteristics. The conservation of the native structure of the entrapped antigen was confirmed by detecting its enzymatic activity after release from microparticles. A single intraperitoneal immunization of mice with rSm28GST entrapped in microparticles resulted in a specific antibody response, which remained high for at least 7 months. The analysis of the isotype profile indicated that immunized mice primarily produced anti-rSm28GST immunoglobulin (Ig) G1 with the coexistence of lower IgG2a and IgG2b levels. Finally, the recognition of the major epitopic regions and the neutralization of the enzymatic activity of the rSm28GST by the antisera confirmed the specificity of the response against the native structure of the antigen. These results confirmed the integrity of the entrapped antigen. Moreover, our results supported the hypothesis that the duration of antigen release is the limiting factor for the duration of antibody production. Indeed, the use of polymers characterized by different molecular weights allowed us to modify the duration of the immune response. Together, these results demonstrated that microencapsulation of an antigen by spray-drying preserved its crucial characteristics required to generate an effective humoral immune response after a single-dose administration.

Animals↗
PubMed2000

CpG motifs induce Langerhans cell migration in vivo.

Cytosine-guanosine (CpG) oligonucleotide (CpG-oligo) sequences are immunostimulatory motifs that are present in bacterial DNA and their presence in plasmids might contribute to the immune response generated by DNA vaccination. The cell targets of CpG motifs in vivo have not been characterized yet. In this report we assessed the in vivo effects of CpG motifs on Langerhans cells (LC) migration. We showed that intradermal injection of 10 microg of CpG-containing oligonucleotides in mouse ear induced the local depletion of LC within 2 h of exposure as shown by CD11c and Ia immunohistological staining. To demonstrate that LC depletion was due to LC migration, CpG oligonucleotides were injected into the explants ex vivo, and the CD11c(+) cells emigrating from the cultured isolated skin within medium were evaluated by immunostaining and FACS analysis. Our findings demonstrate that CpG motifs induce LC/dendritic cell (DC) migration out of the skin. To assess whether CpG motifs may act directly on LC/DC to induce their emigration we next analyzed the effects of CpG motifs in vitro on the expression of adhesion molecules involved in LC/DC migration. The results of these experiments show that alpha(6) integrins, E-Cadherin, ICAM-1, CD11b and CD11c were differentially regulated upon CpG-oligo treatment of immortalized DC. CpG treatment (10 microg/ml for 8 h) resulted in a 100% increase in ICAM-1 staining intensity, a 50% decrease in E-Cadherin staining and a 25% decrease in alpha(6) integrins staining, while no changes in the levels of CD11b and CD11c expression were recorded. Changes in adhesion molecule expression were mirrored by concomitant changes in the cell morphology that included cell depolarization, the appearance of filopods and loss of adherence. This study provides the first in vivo evidence that CpG motifs signal the migration of LC from the epidermis.

Animals↗
PubMed2000

Tetanus toxin fragment C expressed in live Salmonella vaccines enhances antibody responses to its fusion partner Schistosoma haematobium glutathione S-transferase.

Tetanus toxoid has been used widely as an adjuvant. The atoxic fragment C from tetanus toxin (TetC) is potently immunogenic when expressed in Salmonella vaccine strains and has been used as a fusion partner for antigens (Ag). However, there has been no formal comparison of the immunomodulatory impact of TetC on its fusion partners. In this study, we have addressed this important issue. The protective 28-kDa glutathione S-transferase (GST) from Schistosoma haematobium (Sh28GST) was expressed either as a fusion to TetC or as the full-length Sh28GST alone in a nonvirulent aroA-attenuated strain of Salmonella enterica serovar Typhimurium. The Sh28GST proteins were soluble and stably expressed in Salmonella, as evaluated by Western blotting with TetC and/or Sh28GST antisera. Mice were immunized orally with a single dose of the live recombinant Salmonella. The constructs were stable in mice but, dramatically, only the strain expressing the TetC-Sh28GST fusion elicited significant antibody (Ab) responses directed against Sh28GST as determined by enzyme-linked immunosorbent assay. An analysis of the isotype profiles showed that these mice also produced anti-Sh28GST immunoglobulin A and GST-neutralizing assays revealed high levels of neutralizing Abs in sera. These are important correlates of protection in schistosomiasis. In addition, stimulation of spleen cells from immunized mice with Sh28GST Ag showed that both strains, expressing Sh28GST alone or the TetC-Sh28GST fusion, were able to stimulate the secretion of Th1-related cytokines (gamma interferon and interleukin 2) to comparable levels. Thus, TetC has modulated the immune responses generated against its fusion partner, Sh28GST, by markedly enhancing the Ab responses elicited. These results have important implications in the rational development of live vaccines.

Adjuvants, Immunologic↗
PubMed2000

[Predictive ultrasonographic criteria for portal hypertension due to Schistosoma mansoni in a recently established endemiz zone].

The first cases of Schistosoma mansoni infection were reported in the Senegal River Basin ten years ago. Today endemicity is so high that prevalence rates exceed 90 p. 100 in some areas. Schistosomiasis sometimes goes undiagnosed until the occurrence of portal hypertension with rupture of esophageal varices. Endoscopy is the gold standard for detection of esophageal varices but it is impractical in remote areas. Ultrasonography has been proposed as a non-invasive alternative. The purpose of this study is to describe the results of simultaneous endoscopic and ultrasonographic assessment in 101 subjects from the Richard-Toll area of the Senegal River Basin. Findings showed that severe forms of schistosomiasis complicated by portal hypertension were already present in the region less 10 years after description of the first case. This study also proposes a diagnostic score for portal hypertension based on ultrasonographic findings. The features included in this score are thickening of portal vessel walls, portal vessel diameter, and collapsed appearance of the splenic vein during inspiration. In our hands this score allowed reliable prediction of the development of esophageal varices. Ultrasonography is a good tool for identifying severe forms of schistosomiasis. It should be useful for routine screening in recently established endemic zones.

Adolescent↗
PubMed1999

Cellular immune responses of a Senegalese community recently exposed to Schistosoma mansoni: correlations of infection level with age and inflammatory cytokine production by soluble egg antigen-specific cells.

A recently reported epidemic of Schistosoma mansoni infection in Senegal provided an opportunity to study the dynamics of the development of immunity to human schistosomiasis. We report here on the cell-mediated immune response in a population of 99 females and 95 males, with particular emphasis on the relationship between intensity of infection and age. We found that the intensity of infection correlated negatively with age in females but not in males. In men and women, both Th1- and Th2-type cytokines were detected upon in vitro stimulation of PBMCs with soluble egg antigen (SEA) or soluble adult worm antigens (SWAP). In the female group, SEA-induced PBMC proliferation was associated with the production of IFN-gamma, IL-2 and IL-5, all of which correlated negatively with intensity of infection. Most cytokine production correlated positively with age. Spontaneous production of TNF-alpha, IL-6 and IL-10 was higher in the infected population than in an uninfected control group. Our results suggest that immunity to infection could be more pronounced in the female population and associated with a Th0/1 + 2 pattern of cytokine secretion mediated by soluble egg antigen (SEA).

Adolescent↗
PubMed1999

Control of schistosomiasis pathology by combination of Sm28GST DNA immunization and praziquantel treatment.

Today the control of schistosomiasis infection relies only on the use of praziquantel (PZQ) chemotherapy. However, PZQ treatment cannot prevent reinfection and progressive development of the pathology. We assessed in a mouse model the efficiency of a combined therapy, based on the combination of PZQ chemotherapy with Schistosoma mansoni 28-kDa glutathion S-transferase (Sm28GST) DNA vaccination, designed to limit the pathology. Following this combined therapy, the long-term survival of the mice was significantly enhanced in comparison with the survival of mice either vaccinated only or treated with PZQ only. In addition, the development of the pathology observed in the control groups was almost completely prevented in the vaccinated-PZQ-treated mice and was associated with a dramatic reduction of egg deposition in the tissues. We showed that PZQ treatment induced the unmasking of the native GST enzyme at the surface of the worms, thus permitting its neutralization by the antibodies raised by DNA immunization. This study provides insights into the synergistic mechanisms involved in an immunointervention strategy associated with chemotherapy for the control of a chronic infection and its associated pathology.

Animals↗
PubMed1999

Single-dose mucosal immunization with biodegradable microparticles containing a Schistosoma mansoni antigen.

The purpose of this work was to assess the immunogenicity of a single nasal or oral administration of recombinant 28-kDa glutathione S-transferase of Schistosoma mansoni (rSm28GST) entrapped by poly(lactide-co-glycolide) (PLG)- or polycaprolactone (PCL)-biodegradable microparticles. Whatever the polymer and the route of administration used, the equivalent of 100 microg of entrapped rSm28GST induced a long-lasting and stable antigen-specific serum antibody response, with a peak at 9 to 10 weeks following immunization. Isotype profiles were comparable, with immunoglobulin G1 being the predominant isotype produced. The abilities of specific antisera to neutralize the rSm28GST enzymatic activity have been used as criteria of immune response quality. Pooled 10-week sera from mice receiving PLG microparticles by the nasal or oral route neutralized the rSm28GST enzymatic activity, whereas sera of mice receiving either PCL microparticles, free rSm28GST, or empty microparticles inefficiently neutralized this enzymatic activity. Finally, this study shows that a single administration of these microparticles could provide distinct and timely release pulses of microencapsulated antigen, which might greatly facilitate future vaccine development.

Administration, Intranasal↗
PubMed1998

Homologous and heterologous protection after single intranasal administration of live attenuated recombinant Bordetella pertussis.

While single-dose mucosal immunization is best achieved by the use of attenuated live microorganisms, attenuation generally results in decreased immunogenicity. We attenuated Bordetella pertussis by the deletion of the pertussis toxin gene. A single intranasal administration of this strain protected against subsequent challenge as well as did the parent strain and better than immunization with commercial vaccine. Unexpectedly, this attenuation resulted in increased immunogenicity against the protective antigen filamentous hemagglutinin (FHA). In addition, immunogenicity was also enhanced against the Schistosoma mansoni Sm28GST genetically fused to FHA, resulting in protection against the parasite, as characterized by a reduction in worm burden and egg charge, after a single intranasal administration. Thus, attenuated recombinant B. pertussis strains are promising vectors for the simultaneous protection against pertussis and heterologous diseases by a single intranasal administration.

Adhesins, Bacterial↗
PubMed1998

Human IgE responses to rSm22.6 are associated with infection intensity rather than age per se, in a recently established focus of Schistomiasis mansoni.

In studies of schistosomasis mansoni-endemic communities, individuals with IgE responses to a 22 kD adult worm antigen (rSm22.6) suffered lower intensities of reinfection after treatment. It is of interest to define the factors that lead to the production of rSm22.6-specific IgE because it is a marker for resistant individuals and it may be involved in the development of resistance to reinfection. In endemic populations rSm22.6-specific IgE increases linearly with age. However, it is not possible to distinguish between age per se and 'history of infection' in endemic populations because individuals are exposed to the parasite at an early age. We have, therefore, quantified pre- and post-treatment isotype responses to rSm22.6 in a comparatively 'epidemic' Senegalese community where the patients were infected at different ages and where pre-treatment intensity of infection can be taken as a reasonable measure of antigen exposure. Post-treatment isotype responses to rSm22.6 correlated positively with pre-treatment intensities of infection but were not shown to be related to age. IgG1, IgG4 and IgE responses to rSm22.6 were significantly higher after treatment with the difference increasing with the pre-treatment level of infection. These results from a recently established focus of infection suggest that isotype responses to rSm22.6 are antigen-exposure dependent rather than dependent on age per se.

Adolescent↗
PubMed1998

Systemic and mucosal immune responses after intranasal administration of recombinant Mycobacterium bovis bacillus Calmette-Guérin expressing glutathione S-transferase from Schistosoma haematobium.

A major goal of current vaccine development is the induction of strong immune responses against protective antigens delivered by mucosal routes. One of the most promising approaches in that respect relies on the use of live recombinant vaccine carriers. In this study, Mycobacterium bovis BCG was engineered to produce an intracellular glutathione S-transferase from Schistosoma haematobium (Sh28GST). The gene encoding Sh28GST was placed under the control of the mycobacterial hsp60 promoter on a replicative shuttle plasmid containing a mercury resistance operon as the only selectable marker. The recombinant Sh28GST produced in BCG bound glutathione and expressed enzymatic activity, indicating that its active site was properly folded. Both intraperitoneal and intranasal immunizations of BALB/c mice with the recombinant BCG resulted in strong anti-Sh28GST antibody responses, which were enhanced by a boost. Mice immunized intranasally produced a mixed response with the production of Sh28GST-specific immunoglobulin G1 (IgG1), IgG2a, IgG2b, and IgA in the serum. In addition, high levels of anti-Sh28GST IgA were also found in the bronchoalveolar lavage fluids, demonstrating that intranasal delivery of the recombinant BCG was able to induce long-lasting secretory and systemic immune responses to antigens expressed intracellularly. Surprisingly, intranasal immunization with the BCG producing the Sh28GST induced a much stronger specific humoral response than intranasal immunization with BCG producing the glutathione S-transferase from Schistosoma mansoni, although the two antigens have over 90% identity. This difference was not observed after intraperitoneal administration.

Administration, Intranasal↗
PubMed1998

Bordetella pertussis filamentous hemagglutinin enhances the immunogenicity of liposome-delivered antigen administered intranasally.

In an attempt to increase the immunogenicity of mucosally delivered antigens, we incorporated the Bordetella pertussis filamentous hemagglutinin (FHA) adhesin into liposomes containing the glutathione S-transferase of Schistosoma mansoni (Sm28GST) as a model antigen. Outbred mice immunized twice intranasally with liposomes containing a constant suboptimal dose of Sm28GST and increasing doses of FHA produced anti-Sm28GST antibodies in a FHA dose-dependent manner. The addition of 3 microg of FHA to the liposomes induced more than 10-fold-higher anti-Sm28GST antibody titers, compared to those induced by liposomes without FHA. The presence of FHA did not alter the nature of the humoral immune response, and the sera contained anti-Sm28GST immunoglobulin G1 (IgG1), IgG2a, and IgG2b. However, anti-Sm28GST IgA was only detected when at least 3 microg of FHA was added to the preparation. These results show a promising potential for FHA to enhance the immunogenicity of mucosally administered antigens incorporated into liposomes.

Adhesins, Bacterial↗