193 results on '"Louis Chedid"'
Search Results
2. Synergistic Effects Between Recombinant Interleukin-2 and the Synthetic Immunomodulator Murabutide: Selective Enhancement of Cytokine Release and Potentiation of Antitumor Activity
- Author
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George M. Bahr, Edith Darcissac, Philippe Pouillart, and Louis Chedid
- Subjects
Combination therapy ,Fibrosarcoma ,medicine.medical_treatment ,Molecular Sequence Data ,Immunology ,Antineoplastic Agents ,In Vitro Techniques ,Pharmacology ,Biology ,Proinflammatory cytokine ,Mice ,Therapeutic index ,Adjuvants, Immunologic ,Antigens, Neoplasm ,Reference Values ,Interferon ,In vivo ,Histocompatibility Antigens ,Virology ,Antineoplastic Combined Chemotherapy Protocols ,medicine ,Animals ,Humans ,Mice, Inbred BALB C ,Base Sequence ,Drug Synergism ,Cell Biology ,In vitro ,Cytokine ,Toxicity ,Leukocytes, Mononuclear ,Cytokines ,Interleukin-2 ,Female ,Acetylmuramyl-Alanyl-Isoglutamine ,medicine.drug - Abstract
The use of interleukin-2 (IL-2) in the treatment of cancer has shown limited efficacy and dose-limiting toxicity. Combination therapy with other cytokines and/or chemotherapeutic agents has been attempted to enhance the antitumor activity and to reduce the effective therapeutic dose of IL-2. We recently showed, in vitro and in vivo, a synergistic activity between the synthetic immunomodulator murabutide, which is in clinical stage of development, and another therapeutic cytokine, interferon-alpha (IFN-alpha). The present study was performed to assess a possible potentiation of the biologic activities of IL-2 by its association with murabutide. Human PBMC stimulated in vitro with IL-2 and murabutide showed synergistic levels of induced mRNA accumulation and protein secretion for IFN-gamma, IL-12, and colony-stimulating factors (CSFs). No such effects were obtained on the induction of most inflammatory cytokines, including IL-6, IL-8, and tumor necrosis factor alpha (TNF-alpha). Furthermore, the combined administration of murabutide with IL-2 into Meth-A sarcoma-bearing mice resulted in a very significant tumor inhibition as well as in complete tumor regression in nearly 70% of the treated mice. Under the same conditions, treatment with either compound separately had little or no antitumor effect. These preclinical findings will be pursued by the evaluation of the clinical tolerance and biologic activity of the murabutide/IL-2 combination therapy in cancer patients.
- Published
- 1996
3. Immunopharmacological activities and clinical development of muramyl peptides with particular emphasis on murabutide
- Author
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Edith Darcissac, Louis Chedid, Dorian Bevec, P. Dukor, and George M. Bahr
- Subjects
Male ,medicine.drug_class ,medicine.medical_treatment ,Immunology ,Biology ,Immunoglobulin E ,Immunostimulant ,Proinflammatory cytokine ,Mice ,chemistry.chemical_compound ,Immune system ,Adjuvants, Immunologic ,In vivo ,medicine ,Animals ,Humans ,Endothelium ,Receptors, Cytokine ,Cells, Cultured ,Inflammation ,Pharmacology ,Interferon-alpha ,Biological activity ,Shock, Septic ,Cytokine ,chemistry ,biology.protein ,Female ,E-Selectin ,Acetylmuramyl-Alanyl-Isoglutamine ,Cell Adhesion Molecules ,Muramyl dipeptide - Abstract
Certain immunopharmacological activities of muramyl peptides have been associated with inflammatory and undesirable side-effects typically observed following the administration of the prototype molecule muramyl dipeptide. This activity is now demonstrated not to be linked to a direct activation of inflammatory processes in endothelial cells. Neither MDP nor other structural derivatives were able to induce inflammatory cytokines release or E-selectin gene expression in cultured human umbilical vein endothelial cells. However, oral administration of muramyl peptides has been reported to induce certain biological effects, including the downregulation of anamnestic, antigen-specific IgE responses, which are not observed following parenteral administration. We elaborate on these findings and extend them to show the efficacy of a new muramyl peptide in suppressing polyclonally induced serum IgE levels in anti-IgD-treated mice. The comparative effects of muramyl peptides, selected for clinical development, on the induction of cytokines in human whole blood are then presented at the level of mRNA accumulation and protein secretion. Moreover, the cytokine profile induced in vitro and in vivo by the combination of the safe immunostimulant, Murabutide, with interferon-alpha is examined. This combination reveals a selective and beneficial synergistic activity and induces anti-inflammatory cytokines in the absence of synergistic toxicity. The potential and the implications for the use of a therapeutic combination of an immunostimulant with a cytokine are discussed.
- Published
- 1995
4. Targeting of GM2-bearing tumor cells with the cytolytic Clostridium perfringens delta toxin
- Author
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Joseph E. Alouf, Colette Jolivet-reynaud, Louis Chedid, Jaime Estrada, and Leigh A West
- Subjects
Cancer Research ,Clostridium perfringens ,Mice, Inbred A ,Bacterial Toxins ,Mice, Nude ,Antineoplastic Agents ,G(M2) Ganglioside ,Spleen ,medicine.disease_cause ,Cell Line ,Hemolysin Proteins ,Membrane Lipids ,Mice ,In vivo ,Neuroblastoma ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,Drug Interactions ,Tissue Distribution ,Pharmacology (medical) ,Cytotoxicity ,Pharmacology ,Mice, Inbred BALB C ,Toxin ,Chemistry ,Melanoma ,Neoplasms, Experimental ,medicine.disease ,Molecular biology ,Lymphoma ,Cytolysis ,medicine.anatomical_structure ,Oncology ,Injections, Intravenous - Abstract
The cytolytic Clostridium perfringens delta toxin lyses selectively cells which express ganglioside GM2. In this study, we investigated whether delta toxin can be used to characterize GM2 on tumor cell membranes and as an antitumor agent. The sensitivity to lysis by delta toxin of various murine and human malignant cell lines and also normal tissues was quantified using a 51Cr-release assay. The cytotoxicity titers were correlated with the 125I-labeled toxin binding capacity of sensitive and insensitive cells. Seven of eight human melanomas tested were lysed by the toxin and, of these, four were very sensitive (cytotoxicity titers below 12 ng of toxin). All neuroblastomas, gliomas and the retinoblastoma tested were lysed with 3–18 ng of toxin. Three of six carcinomas and one of two sarcomas were also very sensitive (cytotoxicity titers 0.6–15 ng) whereas leukemias and lymphoma cells were insensitive. Normal human tissues were insensitive (erythrocytes, skin fibroblasts) or poorly sensitive (brain, lung, spleen). The in vivo antitumor activity of delta toxin was tested in tumor-bearing mice. Daily intra-tumor injections of 0.5–1 mg of toxin for 4–5 days in carcinoma Me180- and melanoma A375-bearing nude mice, and neuroblastoma C1300-bearing A/J mice significantly inhibited tumor growth for 12–36 days. Intravenous administration of 100 ng of toxin per day for 5 days in Me180- bearing nude mice and C1300-bearing A/J mice gave significant inhibition of tumor growth only during the treatment period, and 10 injections of the same dose of toxin had no significant effect on SK-MEL28, a tumor lacking GM2.
- Published
- 1993
5. Production and Enhanced Anti-tumor Activity of Tumor Necrosis Factor in Mice Treated with Cyclophosphamide
- Author
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Gilles Riveau, Jeanne L. Becker, Louis Chedid, Yoshihiro Noso, and F Audibert
- Subjects
Lipopolysaccharides ,Cancer Research ,medicine.medical_specialty ,Necrosis ,Mouse ,Lipopolysaccharide ,Combination therapy ,Tumor necrosis factor ,Ratón ,Mice, Nude ,Article ,Leukocyte Count ,Mice ,chemistry.chemical_compound ,Nude mouse ,Leukocytopenia ,Internal medicine ,Antineoplastic Combined Chemotherapy Protocols ,Animals ,Medicine ,Anti‐tumor activity ,Cyclophosphamide ,Triglycerides ,biology ,Tumor Necrosis Factor-alpha ,business.industry ,Drug Synergism ,biology.organism_classification ,Endocrinology ,Oncology ,chemistry ,Tumor necrosis factor alpha ,Sarcoma, Experimental ,medicine.symptom ,business ,Acetylmuramyl-Alanyl-Isoglutamine ,Spleen ,Muramyl dipeptide - Abstract
We demonstrated recently that the production of tumor necrosis factor (TNF) is induced in normal mice and in the immunosuppressed nude mouse model by the administration of muramyl dipeptide (MDP) derivatives followed by endotoxin (lipopolysaccharide). In the present study, the ability of this treatment to induce the production of TNF in mice receiving cyclophosphamide (CY) was examined. Two days following treatment with high‐dose CY (250 mg/kg), mice exhibited leukocytopenia and drastically reduced splenic weight. However, these animals remained capable of producing TNF, albeit at lower levels, when treated with MDP derivatives and lipopolysaccharide (LPS), particularly when the lipophilic analogue MDP‐dipalmitoyl glycerol (GDP) was utilized. TNF was also induced by the administration of MDP‐GDP and LPS to Meth A sarcoma‐bearing mice treated with this dose of CY. Furthermore, in all animals receiving this combination therapy, sarcoma necrosis and complete regression were obtained without any sign of tumor regrowth. A dose of 100 mg/kg CY was not effective for inhibiting tumor regrowth under the same experimental conditions. These results demonstrated that the anti‐tumor activity of endogenously induced TNF is potentiated by combined therapy with a high dose of CY.
- Published
- 1990
6. Muramyl Dipeptide Inhibits Replication of Human Immunodeficiency Virus in Vitro
- Author
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W Lange, K N Masihi, B Rohde-Schulz, and Louis Chedid
- Subjects
Lymphocyte ,Immunology ,HIV Core Protein p24 ,Gene Products, gag ,Endogeny ,Biology ,Virus Replication ,Virus ,Microbiology ,chemistry.chemical_compound ,Colony-Stimulating Factors ,Antigen ,Virology ,parasitic diseases ,medicine ,Humans ,Cells, Cultured ,Viral Core Proteins ,HIV ,In vitro ,Reverse transcriptase ,body regions ,Dideoxyadenosine ,Infectious Diseases ,medicine.anatomical_structure ,chemistry ,Acetylmuramyl-Alanyl-Isoglutamine ,Muramyl dipeptide - Abstract
In the search for compounds capable of inducing endogenous production of colony-stimulating factor (CSF) and possessing activity against human immunodeficiency virus (HIV), an immunomodulator, muramyl dipeptide (MDP), was investigated. MDP can enhance monocyte-macrophage CSF in serum and promote nonspecific resistance against a variety of microbial pathogens. MDP exhibited an inhibitory activity against HIV infection of CD4+ H9 lymphocytes and U937 monocytoid cells. An inhibitor of viral reverse transcriptase, 2', 3'-dideoxyadenosine, produced potent inhibition in cultures which were similarly infected with HIV. MDP could partially reduce antigen production in persistently HIV-infected KE37/1 lymphocyte cultures.
- Published
- 1990
7. Polyvalent synthetic vaccines: relationship between T epitopes and immunogenicity
- Author
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L.D. Lise, M. Jolivet, Louis Chedid, F Audibert, Hélène Gras-Masse, and André Tartar
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T-Lymphocytes ,Guinea Pigs ,Molecular Sequence Data ,Biology ,Epitope ,Microbiology ,Epitopes ,Antigen ,parasitic diseases ,Animals ,Amino Acid Sequence ,B-Lymphocytes ,Vaccines ,Vaccines, Synthetic ,General Veterinary ,General Immunology and Microbiology ,Polyvalent Vaccine ,Immunogenicity ,Public Health, Environmental and Occupational Health ,Virology ,Circumsporozoite protein ,Infectious Diseases ,Antibody Formation ,Humoral immunity ,biology.protein ,Molecular Medicine ,Female ,Bacterial antigen ,Antibody ,Peptides - Abstract
Three different synthetic polyvalent vaccines have been constructed by conjugating four synthetic peptides without any carrier protein. The peptides were copy fragments of two bacterial antigens ( Streptococcus pyogenes M protein and diphtheria toxin), two parasitic antigens (circumsporozoite protein of Plasmodium falciparum and Plasmodium knowlesi ), and one viral antigen (hepatitis B surface antigen). Outbred guinea-pigs immunized with polyvalent vaccine containing streptococcal, diphtheric, P. knowlesi and hepatitis peptides raised high specific antibody response against the four specificities. Individual T cell analysis demonstrated that hepatitis peptide bears a T dominant epitope. A similar immune response was obtained with a second polyvalent vaccine where the P. knowlesi peptide had been replaced by the P. falciparum peptide. In both experiments the malarial peptides behave like pure B epitopes. Prediction of immunodominant helper T-cell antigenic sites were performed with the five peptides using computer algorithm. Hepatitis and diphtheric peptides were selected whereas the streptococcal peptide was rejected although it can experimentally contain a T epitope. To confirm this result animals were immunized with a third polyvalent vaccine which does not contain the hepatitis peptide. No T cell proliferation or antipeptide antibodies were detected. These results demonstrate that the cooperative immune response requires a certain degree of antigenic complexity for the induction of antibody response.
- Published
- 1990
8. Selective induction of CD11a,b,c/CD18 and CD54 expression at the cell surface of human leukocytes by muramyl peptides
- Author
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George M. Bahr, Monique A. Parant, Louis Chedid, Gilles Riveau, and Edith Darcissac
- Subjects
Adult ,Lipopolysaccharides ,Adolescent ,Immunology ,Molecular Sequence Data ,CD11c ,chemical and pharmacologic phenomena ,Transferrin receptor ,Biology ,chemistry.chemical_compound ,Adjuvants, Immunologic ,Antigens, CD ,Receptors, Transferrin ,medicine ,Leukocytes ,Humans ,RNA, Messenger ,Receptor ,Cell adhesion ,Base Sequence ,CD11 Antigens ,Receptors, IgE ,Monocyte ,CD23 ,hemic and immune systems ,Middle Aged ,Intercellular Adhesion Molecule-1 ,Molecular biology ,Antigens, Differentiation, B-Lymphocyte ,medicine.anatomical_structure ,Integrin alpha M ,chemistry ,CD18 Antigens ,Muramic Acids ,biology.protein ,Acetylmuramyl-Alanyl-Isoglutamine ,Muramyl dipeptide ,Biomarkers - Abstract
Muramyl dipeptide (MDP), murametide, and murabutide which belong to the family of the immunoadjuvant muramyl dipeptides were applied directly to fresh human whole blood and the expression of some surface markers involved in cell adherence in distinct leukocyte populations was investigated. CD11a,b,c/CD18, CD54, CD49d were selected for their involvement in cell adherence, and transferrin receptor (CD71) and low-affinity IgE receptor (CD23) were selected as markers for activated cells. Whereas CD11a was increased only on monocytes, CD11b, CD11c, and CD18 were strongly enhanced on monocytes and polymorphonuclear cells (PMNs) after treatment with MDPs. This increase in membrane expression of integrins, such as CD11b, was not associated with mRNA synthesis, suggesting a mobilization of the CD11b,c/CD18 intracellular pools present in these cells. In contrast, treatment with MDP, murametide, or murabutide enhanced ICAM-1 (CD54) expression on monocyte and PMN cell surface in association with ICAM-1 mRNA synthesis. No variation of CD49d expression was detected on leukocyte surface after incubation with MDPs. Transferrin receptor (CD71) expression and low-affinity receptor for IgE (CD23) expression were increased on monocyte only after incubation with LPS used as positive control. Moreover, no observable change in the selected markers was detected on lymphocyte after MDPs or LPS treatment. These results indicate that MDPs seem to act preferentially on monocytes and PMNs in increasing the level of molecules involved in cellular adhesion process, either in provoking the expression of preformed molecules or in inducing their synthesis. This contributes to understanding the mechanism of the activities of muramyl peptides on specific and nonspecific immunity.
- Published
- 1996
9. Enhancement in vivo of the antiinflammatory and antitumor activities of type I interferon by association with the synthetic immunomodulator murabutide
- Author
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Philippe Pouillart, Louis Chedid, and George M. Bahr
- Subjects
Combination therapy ,medicine.medical_treatment ,Immunology ,Anti-Inflammatory Agents ,Drug Evaluation, Preclinical ,Pharmacology ,Antiviral Agents ,Mice ,Adjuvants, Immunologic ,In vivo ,Interferon ,Virology ,Adjuvant therapy ,Concanavalin A ,Medicine ,Animals ,Aspartate Aminotransferases ,Hepatitis ,Mice, Inbred BALB C ,business.industry ,Therapeutic effect ,Alanine Transaminase ,Drug Synergism ,Cell Biology ,medicine.disease ,Cytokine ,Toxicity ,Interferon Type I ,Drug Therapy, Combination ,Female ,Chemical and Drug Induced Liver Injury ,Drug Screening Assays, Antitumor ,business ,Acetylmuramyl-Alanyl-Isoglutamine ,medicine.drug - Abstract
The therapeutic efficacy of type I interferon (IFN) has been reported to vary considerably in different indications. The use of the cytokine as adjuvant therapy has been suggested to enhance its efficacy and reduce the toxicity frequently associated with long-term and high-dose administration. In this study, we have assessed the activity of type I IFN in the protection against and treatment of acute hepatitis induced in mice by the administration of concanavalin-A (ConA). At the same time, we have evaluated the efficacy of the synthetic immunomodulator murabutide when administered alone or in combination with type I IFN to protect against ConA hepatitis and in the treatment of tumors in MethA sarcoma-bearing mice. Our results demonstrate a prophylactic effect as well therapeutic effects of type I IFN and of murabutide in the inflammation-mediated model of liver damage. The use of combination therapy presented enhanced efficacy in inhibiting the ConA-induced elevation of plasma transaminases. Both compounds were found to suppress IFN-gamma mRNA accumulation in the livers of ConA treated mice. This activity is discussed with respect to the mechanism of action of the two immunomodulators. In addition, the combination of murabutide with type I IFN exhibited synergistic antitumor activity that was clearly seen in the significant regression of MethA tumors and resulted in almost 50 percent tumor-free mice. The potential clinical application of combination therapies using a cytokine and a safe immunomodulator is analyzed in terms of enhancing the cytokine efficacy and extending its use to new indications.
- Published
- 1996
10. Enhancement by muramyl peptides of the protective response of interferon-alpha/beta against encephalomyocarditis virus infection
- Author
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George M. Bahr, Louis Chedid, Philippe Pouillart, Francoise Audibert, and Pierre Lefrancier
- Subjects
Male ,medicine.medical_treatment ,Immunology ,Alpha interferon ,Biology ,Virus ,Microbiology ,Cell Line ,chemistry.chemical_compound ,Interferon-gamma ,Mice ,Adjuvants, Immunologic ,In vivo ,medicine ,Cardiovirus Infections ,Animals ,Encephalomyocarditis virus ,Interferon alfa ,Pharmacology ,Drug Synergism ,Immunotherapy ,Interferon-beta ,In vitro ,Cytokine ,chemistry ,Acetylmuramyl-Alanyl-Isoglutamine ,Muramyl dipeptide ,medicine.drug - Abstract
The use of interferon-alpha (IFN-alpha) in the treatment of infectious diseases has shown limited efficacy and dose-limiting toxicity. We have selected safe immunomodulators of the muramyl peptide family with the potential of enhancing the efficacy of IFN-alpha without resulting in increased toxicity. One of these synthetic muramyl dipeptide (MDP) derivatives, namely murabutide which is in a clinical stage of development, has been recently found to synergize with IFN-alpha 2a in the selective induction of anti-inflammatory mediators and to enhance the biological activities of the therapeutic cytokine. The present study was performed to assess the antiviral activity of such muramyl peptides and a possible potentiation of the antiviral activity of IFN-alpha/beta by associated therapy using the classical assay of Encephalomyocarditis virus (EMCV) infection. In vitro, pretreatment of Moloney Sarcoma virus (MSV)-transformed cell line with MDP derivatives followed by treatment with IFN-alpha/beta showed a synergistic protection against the cytopathogenic effect of a subsequent EMCV infection. None of the MSV cultures could be protected by stimulation with muramyl peptides alone. In vivo, all of the muramyl peptide derivatives tested were found to be more potent than the parent molecule MDP in inducing protection against death or in the prolongation of the mean survival time of infected mice. Sequential administration of suboptimal doses of exogenous IFN-alpha/beta and muramyl peptides established a strong antiviral state and considerably improved the protective effect of the cytokine, frequently leading to an abortive infection. Our findings suggest that combination therapy with safe muramyl peptides and IFN-alpha/beta could constitute a highly effective and new regimen for the treatment of viral infections in humans.
- Published
- 1996
11. Protection of ruminants by Pasteurella haemolytica A1 capsular polysaccharide vaccines containing muramyl dipeptide analogs
- Author
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Louis Chedid, Brad DeBey, Kim A. Brogden, Howard D. Lehmkuhl, and Francoise Audibert
- Subjects
Male ,Immunogen ,medicine.medical_treatment ,Pasteurella Infections ,Sheep Diseases ,Biology ,Microbiology ,chemistry.chemical_compound ,Adjuvants, Immunologic ,parasitic diseases ,medicine ,Animals ,Pasteurellosis, Pneumonic ,Mannheimia haemolytica ,Bacterial Capsules ,Sheep ,General Veterinary ,General Immunology and Microbiology ,Immunogenicity ,Pasteurellaceae ,Public Health, Environmental and Occupational Health ,Antibody titer ,biology.organism_classification ,medicine.disease ,Virology ,Antibodies, Bacterial ,body regions ,Infectious Diseases ,chemistry ,Immunoglobulin M ,Immunoglobulin G ,Humoral immunity ,Bacterial Vaccines ,Molecular Medicine ,Female ,Adjuvant ,Pasteurellosis ,Acetylmuramyl-Alanyl-Isoglutamine ,Muramyl dipeptide - Abstract
The capsular polysaccharide (CP) of Pasteurella haemolytica serotype A1 is a poor immunogen for the prevention of pneumonic pasteurellosis of ruminants. To improve CP immunogenicity, vaccines were prepared with 1.0 mg CP dose-1 with and without the synthetic adjuvant, muramyl dipeptide (MDP; range 0.2-1.0 mg) or a lipophilic derivative, MDP-sn-glyceryl-dipalmitoyl (MDP-GDP; range 0.1-1.0 mg). The optimum effective concentration of adjuvant was first determined in lambs and calves and then the efficacy of CP +0.5 mg MDP and CP +1.0 mg MDP-GDP was compared with that of two commercial vaccines in calves. After immunization with CP, antibody titers in lambs and calves were typical of that seen with polysaccharide immunogens and characterized by an early IgM response followed by later IgG1 and IgG2 responses. CP + MDP or MDP-GDP vaccines induced significantly higher IgM, IgG1, and IgG2 titers. After transtracheal challenge of immunity with P. haemolytica serotype A1, extensive pulmonary consolidation containing P. haemolytica (10(6)-10(8) c.f.u. g-1) was seen in all lambs and calves vaccinated with CP alone and was not significantly different (P0.05) from the consolidation and concentrations of organisms in nonvaccinated challenge controls. In lambs, vaccines containing 1.0 mg CP +0.05 mg MDP or MDP-GDP significantly reduced pulmonary consolidation and concentrations of P. haemolytica in lung lesions. In calves, vaccines containing 0.2 mg MDP, 0.5 mg MDP, or 1.0 mg MDP-GDP also significantly reduced pulmonary consolidation and concentrations of P. haemolytica in lung lesions. Vaccines containing CP +0.5 mg MDP and CP +1.0 mg MDP-GDP induced high titer bactericidal antibodies by 7 days and were more efficacious than two commercial vaccines. Potentiation of CP with MDP or MDP-GDP has great promise in furthering the potential of CP as a vaccine immunogen for the prevention of pneumonic pasteurellosis.
- Published
- 1995
12. Selective modulation of lipopolysaccharide-induced death and cytokine production by various muramyl peptides
- Author
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C Le Contel, Monique Parant, Philippe Pouillart, Louis Chedid, F Parant, and G M Bahr
- Subjects
Lipopolysaccharides ,Lipopolysaccharide ,medicine.medical_treatment ,Immunology ,Galactosamine ,Biology ,Microbiology ,chemistry.chemical_compound ,Interferon-gamma ,Mice ,Immune system ,medicine ,Animals ,Interferon gamma ,Interleukin 6 ,Sensitization ,Triglycerides ,Mice, Inbred C3H ,Interleukin-6 ,Tumor Necrosis Factor-alpha ,Drug Synergism ,Shock, Septic ,Infectious Diseases ,Cytokine ,medicine.anatomical_structure ,chemistry ,biology.protein ,Cytokines ,Parasitology ,Tumor necrosis factor alpha ,Female ,Acetylmuramyl-Alanyl-Isoglutamine ,Muramyl dipeptide ,medicine.drug ,Research Article ,Interleukin-1 - Abstract
Pretreatment of animals with the adjuvant muramyl dipeptide enhances both the production of circulating tumor necrosis factor and the sensitivity to the lethal effect of a lipopolysaccharide (LPS) challenge. The present study examined the capacity of various adjuvant muramyl dipeptide derivatives to potentiate responsiveness to LPS administration. Cytokine levels in serum were determined at various time intervals after LPS administration by bioassays and immunoassays; the cytokines examined were tumor necrosis factor, interleukin-1, interleukin-6, and gamma interferon. The time course of cytokine response was not modified by the pretreatment, but most of the levels were strongly enhanced. However, of the four compounds which were found to be potent priming agents, only two caused an increased sensitivity to LPS lethality, showing that elevated titers of cytokines in serum were not correlated with host sensitization. Interestingly, previous studies have shown that these two compounds also display neurobiological properties, implying a possible role of the central nervous system in LPS lethality. However, two hydrophilic derivatives with low activity as priming agents were capable of decreasing the toxicity of LPS when given after the challenge in galactosamine-sensitized mice. These results illustrate the diversity of responses elicited by immunological priming. They raise unanswered questions on the importance of endogenous mediators in the pathophysiological alterations during toxic shock.
- Published
- 1995
13. Modulation of the immunosuppressive activity of CKS-17, a synthetic retroviral envelope peptide, by muramyl dipeptide
- Author
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Jean-Pierre Simon, Frederick R. Vogel, Marie Claire Gauduin, Louis Chedid, and F Audibert
- Subjects
medicine.medical_treatment ,Immunology ,Molecular Sequence Data ,Retroviridae Proteins, Oncogenic ,Peptide ,Enzyme-Linked Immunosorbent Assay ,Biology ,Lymphocyte Activation ,Complement Hemolytic Activity Assay ,Virus ,chemistry.chemical_compound ,Mice ,Viral Envelope Proteins ,In vivo ,Virology ,medicine ,Animals ,Amino Acid Sequence ,Cells, Cultured ,chemistry.chemical_classification ,Immunosuppression Therapy ,B-Lymphocytes ,Mice, Inbred BALB C ,Biological activity ,Immunosuppression ,Transmembrane protein ,In vitro ,chemistry ,Biochemistry ,Immunoglobulin M ,Immunoglobulin G ,Molecular Medicine ,Intercellular Signaling Peptides and Proteins ,Female ,Peptides ,Acetylmuramyl-Alanyl-Isoglutamine ,Muramyl dipeptide ,Spleen - Abstract
CKS-17, a heptadecapeptide corresponding to a region highly conserved in retroviral transmembrane proteins is known to be immunosuppressive both in vitro and in vivo when conjugated to a carrier protein. Here we examined the effect of the synthetic adjuvant muramyl dipeptide (MDP) on the immunosuppressive properties of CKS-17-BSA in vitro. MDP was found to abrogate CKS-17-BSA-induced inhibition of both IgM plaque-forming cell responses and antitetanus toxin IgG secretion by BALB/c mouse spleen cells immunized in vivo and in vitro by sheep red blood cells and tetanus toxoid, respectively. In contrast, the CKS-17-BSA suppression of concanavalin A-induced splenocyte proliferation was not abrogated by MDP. The data suggest that muramyl peptides could be useful as immunoadjuvants for vaccines against retrovirus-associated immunosuppressive diseases.
- Published
- 1993
14. MDP Derivatives and Resistance to Bacterial Infections in Mice
- Author
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P. Lefrancier, Monique Parant, C Le Contel, F Parant, and Louis Chedid
- Subjects
chemistry.chemical_compound ,Innate immune system ,chemistry ,Human use ,biology ,Mycobacterium fortuitum ,Biological response modifiers ,biology.organism_classification ,Muramyl dipeptide ,Microbiology - Abstract
Among the numerous biological response modifiers (BRMs) capable of increasing nonspecific immunity to infections, MDP (or muramyl dipeptide) derivatives represent remarkable tools for experimental studies and some of them appear to be suitable for human use because of immunostimulating properties can be separated from some unwanted side effects.
- Published
- 1992
15. Various Aspects of Synergism between Endotoxin and MDPs
- Author
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Louis Chedid and M. Parant
- Subjects
body regions ,Murabutide ,chemistry.chemical_compound ,Chemistry ,Tumor necrosis factor production ,parasitic diseases ,Peptidoglycan ,Pharmacology ,Glycopeptide ,Muramyl dipeptide - Abstract
Muramyl dipeptide (MDP) is a synthetic glycopeptide analog of a part of bacterial peptidoglycan (13). It represents the minimal adjuvant-active structure and has also been shown to stimulate nonspecific resistance in animals subsequently infected (9). These effects have been demonstrated after injecting MDP in saline by different routes. The synthesis of MDP was followed by the preparation of a large number of derivatives with the hope of determining structure-activity relationships (12, 15), or at least of selecting immunostimulating compounds, which did not retain several side effects inherent to MDP administration (6, 24). Such an evaluation has allowed us to select an MDP derivative called Murabutide which is undergoing clinical trials with conventional vaccines after its safety has been established by animal toxicological studies, and in a phase I clinical trial.
- Published
- 1990
16. Obituary Professor Yuichi Yamamura
- Author
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Louis Chedid
- Subjects
Pharmacology ,Philosophy ,Immunology ,Obituary ,Theology - Published
- 1991
17. Action of the immunostimulant murametide on expression of Mac‐1 by human monocytes
- Author
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Edith, Darcissac, primary, Gilles, Rivieau, additional, and Louis, Chedid, additional
- Published
- 1992
- Full Text
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18. Obituary Federico Spreafico (1940–1994)
- Author
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Louis Chedid
- Subjects
Pharmacology ,media_common.quotation_subject ,Immunology ,Art ,Obituary ,Humanities ,media_common - Published
- 1994
19. Influence of murametide on human blood leukocyte functions and their membrane antigens
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Gilles Riveau, Francoise Audibert, and Louis Chedid
- Subjects
Pharmacology ,Membrane ,Antigen ,Human blood ,Chemistry ,Immunology ,Murametide ,Cell biology - Published
- 1991
20. Induction of immunological castration by LHRH administered with a new lipophilic MDP devoid of side effects
- Author
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Louis Chedid, Francoise Audibert, L.D. Lise, Gilles Riveau, and Pierre Lefrancier
- Subjects
Pharmacology ,medicine.medical_specialty ,Endocrinology ,business.industry ,Internal medicine ,Immunology ,medicine ,Immunological castration ,business - Published
- 1991
21. A new non-pyrogenic lipophilic muramylpeptide derivative. I- comparison beteen toxic and antitoxic synergisms with LPS
- Author
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Gilles Riveau, Pierre Lefrancier, E. Lielh, M. Parant, Louis Chedid, C. Lam, J. Hildebrandt, and Francoise Audibert
- Subjects
Pharmacology ,chemistry.chemical_compound ,chemistry ,Immunology ,Organic chemistry ,Derivative (chemistry) - Published
- 1991
22. A new non-pyrogenic muramylpeptide derivative. III- anti-myelotoxic activity
- Author
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J. Zority, K. Thirring, Louis Chedid, M. Parant, and Francoise Audibert
- Subjects
Pharmacology ,chemistry.chemical_compound ,Chemistry ,Immunology ,Medicinal chemistry ,Derivative (chemistry) - Published
- 1991
23. Modulation of interferon-α-induced human monocyte activation by a muramyl dipeptide derivative
- Author
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Gilles Riveau, Louis Chedid, and Edith Darcissac
- Subjects
Pharmacology ,chemistry.chemical_compound ,medicine.anatomical_structure ,Chemistry ,Stereochemistry ,Interferon α ,Monocyte ,Immunology ,medicine ,Muramyl dipeptide ,Derivative (chemistry) - Published
- 1991
24. In vivo and in vitro priming effect of muramyl peptides on subsequent cytokine production by LPS
- Author
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C. Le Contel, Louis Chedid, and Monique Parant
- Subjects
Pharmacology ,Cytokine ,Chemistry ,In vivo ,medicine.medical_treatment ,Immunology ,medicine ,In vitro - Published
- 1991
25. A new non-pyrogenic muramylpeptide derivative. II- Enhancement of non-specific resistance to infections
- Author
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F Parant, Philippe Pouillart, Louis Chedid, E. Schuetze, K. Thirring, M. Parant, and Francoise Audibert
- Subjects
Pharmacology ,chemistry.chemical_compound ,Non specific ,Chemistry ,Immunology ,Combinatorial chemistry ,Derivative (chemistry) - Published
- 1991
26. Immunostimulant activities of a lipophilic muramyl dipeptide derivative and of desmuramyl peptidolipid analogs
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J P Choay, P Lefrancier, Francoise Audibert, E Lederer, M. Level, M. Parant, and Louis Chedid
- Subjects
animal structures ,Fever ,medicine.drug_class ,Guinea Pigs ,Immunology ,Peptide ,Microbiology ,Immunostimulant ,Pneumococcal Infections ,Mice ,chemistry.chemical_compound ,Adjuvants, Immunologic ,Antigen ,medicine ,Animals ,Moiety ,Hypersensitivity, Delayed ,Pseudomonas Infections ,chemistry.chemical_classification ,biology ,Acetylmuramyl-Alanyl-Isoglutamine ,Glycopeptides ,Glycopeptide ,Klebsiella Infections ,carbohydrates (lipids) ,Infectious Diseases ,chemistry ,Biochemistry ,Antibody Formation ,biology.protein ,bacteria ,Parasitology ,Antibody ,Muramyl dipeptide ,Research Article - Abstract
The immunostimulant properties of a new muramyl dipeptide (MDP) derivative bearing a lipophilic moiety on the C-terminal end of the peptide chain are described. It is shown, in particular, that 1,O-(acetylmuramyl-L-alanyl-D-isoglutamine-L-alanyl)-glycerol-3-mycolate had increased immunostimulant activity in comparison with MDP. It induced hypersensitivity even when administered with an antigen in saline, and it gave higher protection against bacterial infections than did MDP. A quite unexpected finding was obtained with the corresponding desmuramyl compound 1,O-(L-alanyl-D-isoglutamine-L-alanyl)-glycerol-3-mycolate, which had no activity in producing humoral antibodies but was just as active as the muramic acid-containing compound in stimulating nonspecific resistance to bacterial infections. It was not pyrogenic. Modifications of the peptide moiety or the lipid moiety of this peptidolipid led to decrease, or even loss, of activity. These results show the importance of the N-acetylmuramyl moiety in MDP for humoral antibody production. The peptidolipid 1,O-(L-alanyl-D-isoglutamine-L-alanyl)-glycerol-3-mycolate is the first member of a new category of nonspecific immunostimulants.
- Published
- 1980
27. Modulation of the growth of murine thymoma cell lines having different lyt-phenotypes by MDP and MDP(D-D): Macrophage-mediated inhibition of in vitro cell growth
- Author
-
Louis Chedid, Nigel C. Phillips, Farrokh Z. Modabber, and George M. Bahr
- Subjects
Thymoma ,T-Lymphocytes ,Indomethacin ,Immunology ,Cell ,Population ,Prostaglandin ,chemical and pharmacologic phenomena ,Biology ,Cell Line ,Mice ,chemistry.chemical_compound ,parasitic diseases ,medicine ,Animals ,Antigens, Ly ,education ,Pharmacology ,Mice, Inbred BALB C ,education.field_of_study ,Cell growth ,hemic and immune systems ,DNA ,Thymus Neoplasms ,Macrophage Activation ,Molecular biology ,Growth Inhibitors ,In vitro ,body regions ,Phenotype ,medicine.anatomical_structure ,Mechanism of action ,chemistry ,Cell culture ,Female ,medicine.symptom ,Acetylmuramyl-Alanyl-Isoglutamine ,Muramyl dipeptide ,Thymidine - Abstract
The ability of N-acetylmuramyl-l-alanyl-d-isoglutamine (MDP) and its adjuvant-inactive stereoisomer, N-acetylmuramyl-d-alanyl-d-isoglutamine, (MDP(D-D)) to inhibit the in vitro growth of 3 murine ascitic thymoma lines, expressing different Lyt-phenotypes, was studied. MDP inhibited the growth of all 3 cell lines. MDP(D-D) inhibited the 2 cell lines expressing Lyt-1+2− or Lyt-1+2+ phenotypes, but not the third cell line which expressed the Lyt-1−2+ phenotype. The ability of MDP or MDP(D-D) to inhibit thymoma growth was lost when the ascitic cell populations were depleted of macrophages. MDP could be replaced by a supernatant derived from an ascitic Lyt-1+2− cell population exposed to MDP. The supernatant required the presence of macrophages for activity. The inhibition by MDP of the growth of the Lyt-1−2+ cell line was prostaglandin synthetase dependent: indomethacin antagonized the inhibitory activity of MDP. The inhibition by MDP of the Lyt-1+2− cell line was partially antagonized by indomethacin, and no antagonism was observed with the Lyt-1+2+ cell line.
- Published
- 1984
28. Monoclonal antibodies to the synthetic adjuvant muramyl dipeptide: Characterization of the specificity
- Author
-
F. Z. Modabber, Ruth Arnon, Michael Sela, Zelig Eshhar, Louis Chedid, R. Ben-Yitzhak, and George M. Bahr
- Subjects
Antigenicity ,medicine.drug_class ,Immunology ,Enzyme-Linked Immunosorbent Assay ,Monoclonal antibody ,Binding, Competitive ,Epitope ,Mice ,Structure-Activity Relationship ,chemistry.chemical_compound ,Antibody Specificity ,parasitic diseases ,medicine ,Animals ,Molecular Biology ,Mice, Inbred BALB C ,Hybridomas ,Dipeptide ,biology ,Antibodies, Monoclonal ,body regions ,chemistry ,Biochemistry ,Monoclonal ,biology.protein ,Female ,Antibody ,Clone (B-cell biology) ,Acetylmuramyl-Alanyl-Isoglutamine ,Muramyl dipeptide - Abstract
Monoclonal antibodies to MDP were prepared by hybridization of NSO myeloma cells with spleen cells of BALB/c mice immunized with MDP conjugated to methyl-BSA. Hybridomas secreting anti-MDP antibodies were selected by the binding activity of their supernates to MDP-A--L using a radioimmunoassay. After cloning in soft agar, the specificities of monoclonal anti-MDP antibodies were assayed by an inhibition of ELISA with various derivatives of MDP. Fine structural analysis of specificity for one such clone (2-4) is reported. This antibody recognizes the N-acetyl-muramic acid (N-Ac-Mur) linked to the dipeptide but not N-Ac-Mur or/and dipeptide alone. The N-Ac group on muramic acid is an important antigenic determinant and the glycopeptide linkage seems to be crucial in presenting the sugar moiety. Conservative substitution of L-Ala (i.e. by L-Ser or L-Val) had no effect on the binding ability to the antibody whereas a radical change, i.e. replacement of L-Ala by L-Pro or N-methyl-L-Ala completely abolished the antigenicity of the molecule. There was no clear correlation between biological activities of various derivatives of MDP and their ability to react with this antibody. Some possible hypotheses explaining this lack of correlation are presented.
- Published
- 1983
29. Macrophage stimulation in vitro by an inactive muramyl dipeptide derivative after conjugation to a multi-poly(DL-alanyl)-poly(L-lysine) carrier
- Author
-
Y. Le Garrec, Louis Chedid, M. Level, P Lefrancier, A Galelli, and M Derrien
- Subjects
Antigenicity ,medicine.medical_treatment ,Immunology ,Lysine ,Mast-Cell Sarcoma ,Biology ,Microbiology ,Cell Line ,Mice ,chemistry.chemical_compound ,Adjuvants, Immunologic ,In vivo ,parasitic diseases ,medicine ,Animals ,Macrophages ,Glycopeptides ,Stereoisomerism ,In vitro ,body regions ,Infectious Diseases ,chemistry ,Biochemistry ,Intercellular Signaling Peptides and Proteins ,Parasitology ,Peptides ,Thymidine ,Acetylmuramyl-Alanyl-Isoglutamine ,Adjuvant ,Cell Division ,Muramyl dipeptide ,Research Article ,Conjugate - Abstract
It has been previously reported that N-acetyl-muramyl-L-alanyl-D-isoglutamine (MDP), which represents the minimal structure that can substitute for mycobacteria in Freund complete adjuvant, activated macrophages in vitro and in vivo. In the present study we show that, in contrast to MDP, the nonadjuvant MDP(DD) stereoisomer has no effect on cytostatic activity of thioglycolate-induced macrophages as measured by uptake of [3H]thymidine. However, surprisingly, after conjugation to an inert carrier, multi-poly(DL-alanyl)-poly(L-lysine), this compound activates macrophages in vitro and becomes at least as effective as MDP. It has also been shown in other studies that after conjugation MDP(DD) remained devoid of antigenicity and of adjuvant activity although such a conjugate could increase resistance to infection. It, therefore, appears that there exists no correlation between the structure required for adjuvant activity and the structure required for macrophage activation or for enhancement of nonspecific immunity.
- Published
- 1980
30. Epitopic suppression in synthetic vaccine models: Analysis of the effector mechanisms
- Author
-
Frederick R. Vogel, Claude Leclerc, M.P. Schutze, and Louis Chedid
- Subjects
Male ,Synthetic vaccine ,Immunology ,Population ,chemical and pharmacologic phenomena ,Biology ,T-Lymphocytes, Regulatory ,Epitope ,Epitopes ,Mice ,Immune system ,Tetanus Toxoid ,Animals ,education ,B-Lymphocytes ,education.field_of_study ,Effector ,Macrophages ,Toxoid ,T-Lymphocytes, Helper-Inducer ,In vitro ,Phenotype ,Mice, Inbred DBA ,Humoral immunity ,Immunization ,Haptens ,Oligopeptides ,Spleen - Abstract
The induction of an immune response against synthetic peptides usually requires the use of an immunogenic carrier. The use of tetanus toxoid (TT) has been proposed for this purpose as it is highly immunogenic and has been used extensively in humans. Previous studies have demonstrated that an epitope-specific suppression of IgG antibody responses occurs when mice previously primed with TT are subsequently immunized with SODP, a haptenic epitope linked to TT. In the present investigation, we characterized the effector populations which regulate anti-SODP antibody responses in TT/TT-SODP immunized mice. In vitro studies showed that epitopic suppression did not arise due to nonspecific suppressor phenomena. Coculture experiments demonstrated that epitopic suppression was partially mediated by suppressor T cells which specifically inhibited the anti-hapten but not the anti-carrier antibody response. The majority of these T cells were shown to possess the Lyt-2+ phenotype. Apart from the T suppressor population we demonstrated a deficiency at the B-cell level which contributed to the total suppressive effect. Epitopic suppression, therefore, resulted from the effects of dual specific suppressor mechanisms.
- Published
- 1987
31. In Vivo and in Vitro Stimulation of Nonspecific Immunity by the -D-p-Aminophenyl Glycoside of N-Acetylmuramyl-L-Alanyl-D-Isoglutamine and an Oligomer Prepared by Cross-Linking with Glutaraldehyde
- Author
-
Edgar Sathe, Chantal Damais, Jean Choay, Monique Parant, Louis Chedid, Francine Parant, Pierre Lefrancier, E Lederer, and Francoise Audibert
- Subjects
Time Factors ,Guinea Pigs ,Dose-Response Relationship, Immunologic ,Spleen ,Aminophenols ,Immunoadjuvant ,Mice ,chemistry.chemical_compound ,Adjuvants, Immunologic ,In vivo ,parasitic diseases ,medicine ,Animals ,Immunology and Allergy ,Glycosides ,Aldehydes ,Acetylmuramyl-Alanyl-Isoglutamine ,Pyrogens ,Glycopeptides ,Immunity ,Klebsiella Infections ,Endotoxins ,body regions ,Infectious Diseases ,medicine.anatomical_structure ,chemistry ,Biochemistry ,Glutaral ,Delayed hypersensitivity ,Female ,Glutaraldehyde ,Thymidine ,Muramyl dipeptide - Abstract
Several biological activities of N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP for muramyl dipeptide), a synthetic immunoadjuvant, are inhibited after glycosidation with p-aminophenol. Thus, this glycoside does not induce an increase humoral antibody response in mice when injected in saline, although it retains its stimulatory effect on circulating antibodies and delayed hypersensitivity after administration in a water-in-oil emulsion. The capacity of MDP to stimulate mouse spleen cells is lost, and, moreover, the analogue is unable to increase nonspecific resistance to infection under conditions where MDP is active. After cross-linking of the beta-D-p-aminophenyl glycoside of MDP with glutaraldehyde, several biological activities of MDP are recovered. Moreover, the cross-linked oligomer (molecular weight, approximately 6,000 daltons) is able to stimulate the uptake of thymidine by spleen cells from a strain of mice weakly responsive to MDP and is more active than MDP in protecting mice against bacterial challenge.
- Published
- 1978
32. Opsonic antibodies evoked by hybrid peptide copies of types 5 and 24 streptococcal M proteins synthesized in tandem
- Author
-
Edwin H. Beachey, A Tarter, Louis Chedid, Jolivet M, Audibert F, Jerome M. Seyer, and Helene Gras-Masse
- Subjects
Streptococcus pyogenes ,Myeloma protein ,Immunology ,Peptide ,Cross Reactions ,Biology ,medicine.disease_cause ,Epitope ,Microbiology ,Bacterial Proteins ,Antigen ,Antibody Specificity ,Opsonin Proteins ,medicine ,Animals ,Immunology and Allergy ,chemistry.chemical_classification ,Antigens, Bacterial ,Myocardium ,Immunogenicity ,Articles ,Antibodies, Bacterial ,Peptide Fragments ,Bacterial vaccine ,chemistry ,Bacterial Vaccines ,Rabbits ,Carrier Proteins ,Bacterial Outer Membrane Proteins - Abstract
The protective immunogenicity of a hybrid peptide containing tandem copies of types 5 and 24 epitopes was investigated. Carboxy-terminal peptides of the cyanogen bromide-derived fragment 7 (CB7) of type 24 M protein were chemically synthesized, and then extended to include the first 20 residues of the amino-terminus of type 5 M protein. When emulsified in CFA and injected into rabbits without conjugation to a carrier, each of the synthetic hybrid peptides, designated S-M5(1-20)-S-CB7(23-35)C and S-M5(1-20)-S-CB(19-34), evoked opsonic antibodies against both types 5 and 24 streptococci without raising heart tissue-crossreactive immunity. These results suggest that tandem hybrid peptides may provide a new approach to the development of multivalent vaccines, not only to different serotypes of group A streptococci but perhaps also to a variety of other infectious agents.
- Published
- 1986
33. Nonspecific activation of murine spleen cells in vitro by a synthetic immunoadjuvant (N-acetyl-muramyl-l-alanyl-d-isoglutamine)
- Author
-
Monique Parant, Louis Chedid, and Chantal Damais
- Subjects
Cell Extracts ,Isoglutamine ,Time Factors ,medicine.medical_treatment ,Immunology ,Mice, Nude ,Stimulation ,Spleen ,Lymphocyte Activation ,Immunoadjuvant ,Mycobacterium ,Mice ,Mice, Inbred AKR ,chemistry.chemical_compound ,Fetus ,Adjuvants, Immunologic ,Pregnancy ,medicine ,Animals ,Mercaptoethanol ,Mice, Inbred BALB C ,biology ,Mycobacterium smegmatis ,Glycopeptides ,biology.organism_classification ,Molecular biology ,In vitro ,Mice, Inbred C57BL ,medicine.anatomical_structure ,chemistry ,Mice, Inbred DBA ,Cattle ,Female ,Thymidine ,Adjuvant - Abstract
We reported previously that synthetic N -acetyl-muramyl- l -alanyl- d -isoglutamine (MDP) displayed marked adjuvant activity but was devoid of mitogenicity in vitro . The data reported here establish that, under different cultural conditions, thymidine uptake and blast cells can be increased by MDP in spleen cells of DBA/2 and Balb/c mouse strains. Optimal responses were obtained on culture in a serum-free medium supplemented with 2-mercaptoethanol for 4 or 5 days. This effect was also obtained with spleen cells of Balb/c nude mice. When the synthetic MDP was compared to a natural water-soluble adjuvant (neo-WSA), extracted from Mycobacterium smegmatis cells, both were found to stimulate [ 3 H] thymidine incorporation by mouse spleen cells. However, with the neo-WSA, the effect peaked on Day 2 and was weak or absent on Days 4 and 5. When the cells were cultured in a medium containing fetal calf serum, neo-WSA activation was completely abolished, while MDP-mediated stimulation was decreased.
- Published
- 1977
34. Central pyrogenic activity of muramyl dipeptide
- Author
-
Gilles Riveau, Louis Chedid, Monique Parant, and Karel Masek
- Subjects
Male ,Hyperthermia ,Fever ,Immunology ,chemical and pharmacologic phenomena ,Pharmacology ,Immunoadjuvant ,chemistry.chemical_compound ,In vivo ,medicine ,Animals ,Immunology and Allergy ,Infusions, Parenteral ,Injections, Intraventricular ,Dipeptide ,Acetylmuramyl-Alanyl-Isoglutamine ,Pyrogens ,Glycopeptides ,Brain ,Articles ,medicine.disease ,Glycopeptide ,chemistry ,Rabbits ,Peptidoglycan ,Muramyl dipeptide ,Body Temperature Regulation - Abstract
Fever can be elicited in the rabbit by the intravenous administration of relatively large doses of a synthetic immunoadjuvant, N-acetylmuramyl-L-alanyl-D-isoglutamine, or muramyl dipeptide (MDP). This response could be mediated by endogenous pyrogen because MDP has been shown to induce their production both in vivo and in vitro. The results reported here show that intracisternal injection of minute amounts of MDP could elevate fever without activating the release of endogenous pyrogen in the plasma or in the cerebrospinal fluid. Moreover, indomethacin inhibited hyperthermia produced by intracerebroventricular administration of MDP. Therefore, our findings argue in favor of a direct effect of the glycopeptide on the thermoregulatory centers besides its indirect effect through the production of leukocytic pyrogen. This molecule apparently represents the minimal requirement for the pyrogenicity of bacterial peptidoglycan because administration, even by the intracerebral route, of a mixture of muramic acid and of its dipeptide moiety did not elicit fever.
- Published
- 1980
35. Muramyl peptides. Variation of somnogenic activity with structure
- Author
-
Jean Choay, Edgar Lederer, Manfred L. Karnovsky, James M. Walter, Louis Chedid, James M. Krueger, and Pierre Lefrancier
- Subjects
Male ,Immunology ,Biology ,Pharmacology ,Muramyl peptide ,Body Temperature ,chemistry.chemical_compound ,Adjuvants, Immunologic ,parasitic diseases ,Animals ,Immunology and Allergy ,Injections, Intraventricular ,Immune Stimulation ,Dose-Response Relationship, Drug ,Acetylmuramyl-Alanyl-Isoglutamine ,Pyrogens ,Electroencephalography ,Biological activity ,Articles ,body regions ,chemistry ,N-monoacetylcystine ,Rabbits ,Sleep Stages ,Muramyl dipeptide - Abstract
Sleep-promoting activities of muramyl dipeptide (MDP) (NAc-Mur-L-ala-D-isogln) and the naturally occurring muramyl peptide(s), factor S, have recently been demonstrated. We now have amplified our understanding of structural requirements for somnogenic activity. The effects of several analogs of MDP on rabbit slow-wave sleep are presented and these results are compared to the dose-response relationship for MDP. Some tentative conclusions as to structural requirements for somnogenic activity are presented; most notably, amidation of the free gamma-carboxyl of MDP and several of its analogs resulted in the loss of somnogenic activity. MDP also can induce febrile and immunostimulatory responses. In the present paper, we show that some analogs possess immunostimulatory and pyrogenic activity but not somnogenic activity, thus suggesting that these biological activities of muramyl peptides may, in part, be mediated by separate mechanisms.
- Published
- 1984
36. Production of antibodies recognizing a hepatitis B virus (HBV) surface antigen by administration of Murabutide associated to a synthetic pre-S HBV peptide conjugated to a toxoid carrier
- Author
-
A.Robert Neurath, Stephen B H Kent, F Audibert, M. Jolivet, Grzegorz Przewlocki, and Louis Chedid
- Subjects
Murabutide ,HBsAg ,Diphtheria Toxoid ,Freund's Adjuvant ,Biophysics ,Aluminum Hydroxide ,Peptide ,Conjugated system ,medicine.disease_cause ,Biochemistry ,Mice ,Viral Proteins ,Adjuvants, Immunologic ,Antigen ,Antibody Specificity ,Tetanus Toxoid ,medicine ,Animals ,Hepatitis B Antibodies ,Molecular Biology ,chemistry.chemical_classification ,Hepatitis B virus ,Mice, Inbred BALB C ,Hepatitis B Surface Antigens ,biology ,Chemistry ,Toxoid ,Cell Biology ,Virology ,Molecular biology ,Peptide Fragments ,biology.protein ,Female ,Antibody ,Acetylmuramyl-Alanyl-Isoglutamine - Abstract
The influence of Murabutide, a muramyl peptide analog, on the response of mice to two synthetic hepatitis B virus antigens was compared with the activity of Al (OH)3 and of FCA. The synthetic peptides represented fragments either of the major component of the hepatitis B surface antigen (HBsAg) or of the pre-S region. They were used either conjugated to toxoid carrier or as a totally synthetic preparation, i.e. copolymerized with a streptococcal peptide. Our results demonstrated that treatment with Murabutide increased the levels of antibodies, modulated their specificity and allowed a better recognition of the natural antigens.
- Published
- 1986
37. Chemically Defined Bacterial Products with Immunopotentiating Activity
- Author
-
F. Audibert and Louis Chedid
- Subjects
Lipopolysaccharides ,Lipopolysaccharide ,medicine.medical_treatment ,Peptidoglycan ,Biology ,Mycobacterium ,Microbiology ,Mice ,chemistry.chemical_compound ,Immune system ,Adjuvants, Immunologic ,medicine ,Animals ,Immunology and Allergy ,Molecular mass ,Polysaccharides, Bacterial ,Succinic anhydride ,Serum Albumin, Bovine ,Infectious Diseases ,Salmonella enteritidis ,chemistry ,Freund's adjuvant ,Antibody Formation ,Toxicity ,Adjuvant - Abstract
The adjuvant activity of two chemically well-defined bacterial products is reviewed: (1) lipopolysaccharides of gram-negative bacillis and their acylated detoxified derivatives, and (2) mycobacterial water-soluble fractions and synthetic analogues. Water-soluble adjuvant can substitute for mycobacteria in Freund's adjuvant, but if it is administered in saline, it has little activity. In contrast, lipopolysaccharide under the same conditions markedly increases the humoral antibody response. However, the use of lipopolysaccharide is limited by its toxicity. Water-soluble adjuvant treated with phthalic or succinic anhydride was shown to be an adjuvant when administered in saline. Furthermore, synthetic M-acetyl-muramyl-L-alanyl-D-isoglutamine also increased the humoral immune response when given in aqueous medium instead of in the usual water-in-oil emulsion. This compound, which has a small molecular weight, is not mitogenic, immunogenic, or toxic in mice, and was shown to have adjuvant activity even when given by the oral route.
- Published
- 1977
38. Enhancement of nonspecific immunity to Klebsiella pneumoniae infection by a synthetic immunoadjuvant (N-acetylmuramyl-L-alanyl-D-isoglutamine) and several analogs
- Author
-
Monique Parant, Louis Chedid, P Lefrancher, Edgar Lederer, Jean Choay, and Francine Parant
- Subjects
Klebsiella pneumoniae ,Injections, Subcutaneous ,Administration, Oral ,Peptidoglycan ,Immunoadjuvant ,Microbiology ,Mice ,Structure-Activity Relationship ,chemistry.chemical_compound ,Adjuvants, Immunologic ,Immunity ,Animals ,Multidisciplinary ,Innate immune system ,biology ,Acetylmuramyl-Alanyl-Isoglutamine ,Immunogenicity ,Glycopeptides ,biology.organism_classification ,Glycopeptide ,Klebsiella Infections ,chemistry ,Injections, Intravenous ,Research Article - Abstract
N-Acetylmuramyl-L-alanyl-D-isoglutamine and four other synthetic adjuvants that are structural analogs of part of the mycobacterial peptidoglycan monomer are shown to enhance the nonspecific immunity of mice infected by Klebsiella pneumoniae. These compounds are active by various routes, including oral administration; they are also effective when administered after challenge. Of the seventeen other analogs tested, none is able to increase significantly resistance to infection, although seven of these molecules are adjuvant-active in saline. Previous results have shown that in contrast to lipopolysaccharides, these synthetic adjuvants are devoid of immunogenicity, mitogenicity, and toxicity in normal or adrenalectomized mice.
- Published
- 1977
39. Role of B-Lymphocytes in Nonspecific Resistance to Klebsiella pneumoniae Infection of Endotoxin-Treated Mice
- Author
-
Monique Parant, Louis Chedid, Galelli Galelli, and Francine Parant
- Subjects
Lipopolysaccharides ,Male ,C57BL/6 ,Klebsiella ,Time Factors ,Hydrocortisone ,Cyclophosphamide ,Klebsiella pneumoniae ,Lymphocyte ,Mice, Nude ,Stimulation ,Biology ,Lymphocyte Activation ,Microbiology ,Lipid A ,Mice ,Mice, Inbred AKR ,medicine ,Animals ,Immunology and Allergy ,Mononuclear Phagocyte System ,B-Lymphocytes ,Mercaptopurine ,biology.organism_classification ,In vitro ,Klebsiella Infections ,Endotoxins ,Mice, Inbred C57BL ,Infectious Diseases ,medicine.anatomical_structure ,Immunology ,lipids (amino acids, peptides, and proteins) ,medicine.drug - Abstract
Lipopolysaccharides (LPS) of gram-negative bacilli are known to protect mice against unrelated bacterial infections and to be nonspecific mitogens of murine bone marrow-derived (B-) lymphocytes. For assessment of the role of these cells in the mechanism of LPS-induced resistance to infection with Klebsielia, various nontoxic mitogens were assayed. In contrast to LPS or lipid A, the nontoxic mitogens did not protect mice. Experiments were also performed with LPS in nude mice and in mice treated with immunosuppressants. Stimulation by LPS was decreased after administration of hydrocortisone or cyclophosphamide under conditions that inhibited the in vitro activation of lymphocytes by mitogens. Moreover, nude mice and mice treated with 6-mercaptopurine were more resistant to Klebsiella than were control mice.
- Published
- 1976
40. Nwsm, A Mitogen from Nocardia Opaca, Specific for Rabbit Bursa Equivalent Cells (1)
- Author
-
C. Damais, B. Cinader, Constantin A. Bona, Louis Chedid, S. Dubiski, R Ciorbaru, and N. Shek
- Subjects
biology ,Immunology ,Rabbit (nuclear engineering) ,Spleen ,Virology ,Molecular biology ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,Polyclonal antibodies ,Mitogen-activated protein kinase ,Nocardia opaca ,biology.protein ,medicine ,Ultrastructure ,Antibody ,Thymidine - Abstract
Treatment of rabbit spleen cells with a water soluble mitogen from Nocardia opaca (NWSM) resulted in the appearance of 30% of cells with the ultrastructural characteristics of plasmocytes and in enhanced thymidine uptake. The extent of incorporation was not diminished by prior complement mediated killing of thymus derived cells with a goat antibody, directed against rabbit thymus lymphocyte antigen (RTLA). The exposure of rabbit spleen cells to NWSM resulted in a polyclonal antibody response. It was concluded that NWSM is a potent mitogen for bursa equivalent lymphoid cells of the rabbit.
- Published
- 1974
41. Nonspecific Resistance to Infection Induced in Mice by a Water-Soluble Adjuvant Derived from Mycobacterium smegmatis
- Author
-
Ronald J. Elin, Louis Chedid, and Sheldon M. Wolff
- Subjects
Male ,Plasmodium berghei ,Klebsiella pneumoniae ,Iron ,medicine.medical_treatment ,Infections ,medicine.disease_cause ,Pneumococcal Infections ,Mycobacterium ,Microbiology ,Mice ,Adjuvants, Immunologic ,Candida albicans ,Streptococcus pneumoniae ,medicine ,Animals ,Immunology and Allergy ,biology ,medicine.diagnostic_test ,Mycobacterium smegmatis ,Candidiasis ,biology.organism_classification ,Corpus albicans ,Klebsiella Infections ,Malaria ,Infectious Diseases ,Serum iron ,Adjuvant - Abstract
The effect of a nontoxic, water-soluble adjuvant (Neo-WSA) from delipidated cells of Mycobacterium smegmatis on the susceptibility of mice to infection with four challenge organisms was studied. An intravenous dose of 1 mg of Neo-WSA per mouse 24 hr before challenge enhanced resistance to infection with a fungus (Candida albicans), a gram-negative bacterium (Klebsiella pneumoniae), and a gram-positive bacterium (Streptococcus pneumoniae). Protection by Neo-WSA was not significant when the mice were challenged with a malarial parasite. Plasmodium berghei. When 1 mg of Neo-WSA was given intravenously to mice 10 min before challenge with C. albicans, protection was significant, but when the same dose was given two or six days prior to challenge, mice were not protected. The concentration of iron in serum had not changed significantly 1 or 24 hr after the intravenous injection of 1 mg of Neo-WSA. Thus Neo-WSA is capable of inducing nonspecific resistance to certain experimental infections in mice. The protection afforded by administration of Neo-WSA 10 min before challenge, the lack of protection afforded by administration of Neo-WSA six days before challenge, and the lack of significant change in the serum iron concentration clearly separate this compound from bacterial endotoxins, which are classical inducers of nonspecific resistance to infection.
- Published
- 1976
42. Influence of helical organization on immunogenicity and antigenicity of synthetic peptides
- Author
-
J.P. Aubert, Hervé Drobecq, M. Jolivet, André Tartar, Hélène Gras-Masse, Louis Chedid, F Audibert, and Edwin H. Beachey
- Subjects
Antigenicity ,Protein Conformation ,Myeloma protein ,Immunology ,Peptide ,Biology ,medicine.disease_cause ,Antibodies ,Mice ,medicine ,Animals ,Antigens ,Molecular Biology ,Peptide sequence ,chemistry.chemical_classification ,Vaccines, Synthetic ,Immunogenicity ,Model protein ,Molecular biology ,Peptide Fragments ,Biochemistry ,chemistry ,Streptococcus pyogenes ,biology.protein ,Female ,Antibody ,Peptides - Abstract
Using cooperative effects of different peptide structures synthesized in tandem, we have induced an α -helical structure in water solution on a peptide which, alone, is unorganized. This structure is particularly relevant in this case as the selected model protein (type 24 M protein of Streptococcus pyogenes ) is an extended coiled-coil system. We were thus able to assess the importance of organization or unorganization of a unique amino acid sequence with regards to its immunogenicity and antigenicity. Although in a classical manner, antibodies cross-reacting with the protein can be obtained with the short, unorganized peptide, we demonstrate that conformation-specific antibodies are raised when longer, organized peptides are used as immunogens.
- Published
- 1988
43. Efficient genetically controlled formation of antibody to a synthetic antigen [poly(LTyr, LGlu)-poly(DLAla)- -poly(LLys)] covalently bound to a synthetic adjuvant (N-acetylmuramyl-L-alanyl-D-isoglutamine)
- Author
-
Michael Sela, Edna Mozes, and Louis Chedid
- Subjects
Immunogen ,Synthetic antigen ,medicine.medical_treatment ,Genes, MHC Class II ,Dose-Response Relationship, Immunologic ,Biology ,Mice ,Immune system ,Adjuvants, Immunologic ,Antigen ,Antibody Specificity ,parasitic diseases ,medicine ,Animals ,Multidisciplinary ,Immunogenicity ,Glycopeptides ,Molecular biology ,body regions ,Antibody Formation ,biology.protein ,Antibody ,Peptides ,Acetylmuramyl-Alanyl-Isoglutamine ,Adjuvant ,Research Article ,Conjugate - Abstract
The synthetic polypeptide antigen poly(LTyr, LGlu)-poly(DLAl)- -poly(LLys)[T,G)-A- -L] was covalently linked to N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP), which is the minimal adjuvant-active structure that can substitute for Mycobacteria in complete Freund's adjuvant. When injected in aqueous solution into mice, the completely synthetic conjugate elicited significant antibody responses specific to (T,G)-A- -L, whereas (T,G,)-A- -L alone administered under the same conditions did not lead to antibody production. The conjugate was much more efficient in eliciting (T,G)-A- -L responses than was a mixture of DMP and (T,G)-A- -L. One hundred micrograms of MDP mixed with 10 micrograms of (T,G)-A- -L resulted in production of (T,g)-A- -L-specific antibodies. However, the titers obtained were much lower than those observed with 10 micrograms of the conjugate, MDP-(T,G)-A- -L, which contained less than 1 microgram of MDP. MDP was enhanced when the mixture was administered in incomplete Freund's adjuvant, the adjuvant did not significantly affect the (T,G)-A- -L-specific antibody responses in mice immunized with MDP-(T,G)-A- -L. The isoelectric focusing pattern of antibodies obtained with MDP-(T,G)-A- -L was similar to that obtained after immunization with (T,G)-A- -L in complete Freund's adjuvant. The pattern of high-responder and low-responder mice to (T,G)-A- -L, the immune response to which is genetically controlled, was retained when MDP-(T,G)-A- -L was used as the immunogen. Conjugation of (T,G)-A- -L was creased the immunogenicity of MDP and affected its biological properties. It is thus possible to obtain efficient immune responses to synthetic polypeptide antigens that produce poor reactions when injected in aqueous solution by conjugating them to small molecular weight synthetic adjuvants.
- Published
- 1980
44. Stimulation of an Enhanced in Vitro Immune Response by a Synthetic Adjuvant, Muramyl Dipeptide
- Author
-
Steven Specter, Roberta Cimprich, Herman Friedman, and Louis Chedid
- Subjects
Immunology ,Immunology and Allergy - Abstract
Various subcellular bacterial fractions are known to enhance immune responses and serve as potent adjuvants. Muramyl dipeptide (MDP), a synthetic adjuvant mimicking a component of mycobacterial cell walls, enhances humoral immunity to soluble antigens and can increase macrophage cytotoxicity toward mastocytoma cells in vitro. In the present study MDP was found to enhance the hemolytic antibody plaque response of normal mouse spleen cells in vitro to SRBC at a level equal to or greater than that induced by Escherichia coli lipopolysaccharide. Furthermore, MDP was found to enhance the antibody response to SRBC nonspecifically in unimmunized spleen cell cultures, suggesting that similar to LPS the synthetic dipeptide may induce a generalized clonal expansion of committed lymphocytes and thus serve as a “polyclonal activator.” MDP also enhanced the immune responsiveness of normal splenocytes to suboptimum concentrations of SRBC, indicating that this material may be useful in enhancing immunity in situations where there would normally be a poor immune response.
- Published
- 1978
45. Increased synthesis of fibrinolytic inhibitor induced by muramyl dipeptide derivatives in human cultured endothelial cells
- Author
-
Louis Chedid, E. Dupuy, M. Terrier, A.M. Dosne, and F. Dubor
- Subjects
Pharmacology ,Activator (genetics) ,Fibrinolysis ,Immunology ,Cell migration ,Biological activity ,Biology ,Urokinase-Type Plasminogen Activator ,Molecular biology ,In vitro ,Endothelial stem cell ,Plasminogen Activators ,Plasminogen Inactivators ,chemistry.chemical_compound ,Adjuvants, Immunologic ,Biochemistry ,chemistry ,Cell culture ,Humans ,Endothelium ,Acetylmuramyl-Alanyl-Isoglutamine ,Plasminogen activator ,Cells, Cultured ,Muramyl dipeptide - Abstract
A decreased fibrinolytic activity induced by bacterial products and some muramyl peptides has been previously demonstrated in macrophages preparations. Since vascular endothelial cells are important for the fibrinolytic balance, we have studied the effects of MDP derivatives on cultured endothelial cells. The supernatant of MDP and murabutide treated cell cultures exhibited an increased fibrinolytic inhibitory activity when tested with urokinase. The MDP(D-D)-treatment had no effect. This increased inhibitory activity was detectable in the supernatant after a 6 h treatment and was suppressed by the addition of puromycine to the cell cultures. Furthermore, the endothelial cell culture supernatant also reduced the lytic activity of the human plasma plasmitogen activator induced by venostasis. This was enhanced by MDP treatment of the cultures. These in vitro results suggested that adjuvant-active muramyl peptides may regulate the fibrinolytic balance at the vessel wall level. This could be of possible significance in the transendothelial cell migration where the role of plasminogen activator(s) has been involved.
- Published
- 1985
46. Effects of natural or synthetic microbial adjuvants on induction of autoimmune thyroiditis
- Author
-
Noel R. Rose, Francoise Audibert, Louis Chedid, Yi Chi M. Kong, and Alvaro A. Giraldo
- Subjects
Lipopolysaccharides ,medicine.medical_specialty ,Lipopolysaccharide ,medicine.medical_treatment ,Immunology ,Mice, Inbred Strains ,Thyroglobulin ,Microbiology ,Thyroiditis ,Autoimmune thyroiditis ,Mice ,Structure-Activity Relationship ,chemistry.chemical_compound ,Adjuvants, Immunologic ,Internal medicine ,parasitic diseases ,medicine ,Animals ,Autoantibodies ,Autoimmune disease ,business.industry ,Thyroid ,Thyroiditis, Autoimmune ,Autoantibody ,medicine.disease ,body regions ,carbohydrates (lipids) ,Infectious Diseases ,medicine.anatomical_structure ,Endocrinology ,chemistry ,Female ,Parasitology ,business ,Acetylmuramyl-Alanyl-Isoglutamine ,Adjuvant ,Research Article - Abstract
Natural and synthetic adjuvants of microbial origin were compared for their capacity to potentiate the induction of experimental autoimmune thyroiditis (EAT) with the autoantigen mouse thyroglobulin (MTg). Regardless of the immunomodulator used, severe thyroiditis was observed only in EAT-susceptible strains of the k haplotype and not in EAT-resistant strains of the d haplotype. Compared to phenol-extracted lipopolysaccharide, a potent adjuvant for enhancing EAT induction, phthalyl-substituted, detoxified lipopolysaccharide, even at doses 15- to 50-fold greater, led to only low anti-mouse thyroglobulin titers and mild thyroid infiltration. The synthetic adjuvant N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) and three of its analogs, N-acetylmuramyl-L-alanyl-D-isoglutamine-L-alanyl-D-glycerol mycolate (MDP-L-Ala-Glyc-Myc), N-acetylmuramyl-L-alanyl-D-glutamyl-(decyl)methyl ester [MDP(decyl)methyl], and N-acetylmuramyl-L-alanyl-D-glutamine-alpha n-butyl ester [MDP-(Gln)-OnBu], designated murabutide, were tested in incomplete Freund adjuvant or in saline. In incomplete Freund adjuvant, MDP-L-Ala-Glyc-Myc was inefficient in inducing EAT, murabutide induced very mild involvement, and MDP and, more so, MDP(decyl)methyl were active but to a lesser degree than CFA. When saline was used, low levels of thyroid infiltration were observed in a few of the MDP-treated animals in only one experiment, whereas no lesions were observed when murabutide was used.
- Published
- 1985
47. Modulation of carrier-induced epitopic suppression by Bordetella pertussis components and muramyl peptide
- Author
-
Thomas W. Klein, M. Jolivet, Francoise Audibert, Claude Leclerc, F.R. Vogel, Louis Chedid, and M.P. Schutze
- Subjects
Synthetic vaccine ,Bordetella pertussis ,Synthetic antigen ,Immunology ,chemical and pharmacologic phenomena ,Pertussis toxin ,complex mixtures ,Epitopes ,Mice ,Tetanus Toxoid ,medicine ,Animals ,Virulence Factors, Bordetella ,Immunosuppression Therapy ,Pertussis Vaccine ,Vaccines, Synthetic ,biology ,business.industry ,Immunogenicity ,Toxoid ,biology.organism_classification ,Endotoxins ,Pertussis Toxin ,Immunoglobulin G ,Pertussis vaccine ,Female ,Carrier Proteins ,business ,Acetylmuramyl-Alanyl-Isoglutamine ,Oligopeptides ,Hapten ,medicine.drug - Abstract
Synthetic antigens employed in experimental synthetic vaccines are generally small haptenic peptides. Therefore, effective immunization with these antigens usually requires the use of an immunogenic carrier. Tetanus toxoid has been proposed for use as a carrier in future synthetic vaccines due to its high immunogenicity and acceptance for human use. Previous studies employing standard hapten/carrier systems such as DNP/KLH have demonstrated, however, that an epitope-specific suppression occurs when mice previously primed with carrier are subsequently immunized with an haptenic epitope conjugated to the same carrier. These same studies have shown that Bordetella pertussis vaccine administered at the time of carrier priming abrogates epitopic suppression. In the present investigation, epitopic suppression was studied in a synthetic vaccine model employing tetanus toxoid as a carrier. Results from these studies indicated that mice primed with tetanus toxoid 1 month before immunization with a peptide-tetanus toxoid conjugate exhibited enhanced secondary anti-tetanus toxin responses but decreased anti-peptide responses. Furthermore, injection of pertussis vaccine or purified B. pertussis toxin or endotoxin at the time of carrier priming could block the establishment of epitopic suppression. Administration of B. pertussis components enhanced antibody responses to both the carrier and the synthetic peptides as compared with responses of control animals. In addition, administration of an adjuvant-active nonpyrogenic derivative of muramyl dipeptide. Murabutide, with carrier priming reduced epitopic suppression of anti-peptide responses. B. pertussis toxin or endotoxin administered to mice previously suppressed by carrier priming with the first injection of carrier-peptide conjugate overcame epitopic suppression with resultant titers of anti-peptide antibody equal to or greater than nonsuppressed controls. These results suggest that the use of adjuvants with future synthetic vaccines may contribute the additional advantage of overcoming epitopic suppression, thus permitting the use of common, well-tolerated carrier systems such as tetanus toxoid in synthetic vaccine preparations.
- Published
- 1987
48. Enhanced oxidative burst without interleukin 1 production by normal human polymorphonuclear leukocytes primed with muramyl dipeptides
- Author
-
C. Jupin, Louis Chedid, M. Parant, and C. Damais
- Subjects
Neutrophils ,Immunology ,Population ,chemical and pharmacologic phenomena ,Stimulation ,In Vitro Techniques ,Biology ,Granulocyte ,chemistry.chemical_compound ,Superoxides ,medicine ,Humans ,Immunology and Allergy ,Centrifugation ,education ,education.field_of_study ,Interleukin ,Biological activity ,Molecular biology ,Respiratory burst ,medicine.anatomical_structure ,chemistry ,Biochemistry ,Acetylmuramyl-Alanyl-Isoglutamine ,Muramyl dipeptide ,Interleukin-1 - Abstract
Purified polymorphonuclear (PMN) cells were obtained from human blood leukocytes by centrifugation on colloidal silica gradients. PMNs could be primed for PMA-triggered oxidative burst by muramyl peptide molecules (MDP) and two of its adjuvant active nonpyrogenic derivatives. The priming effect of MDP could be demonstrated after a 1-h incubation period, whereas monocytes needed an 18-h incubation to produce an enhanced response in the NBT reduction test. Only the monocyte-enriched population was able to produce IL-1 activity after muramyl peptide stimulation. Under such conditions, PMNs neither produced nor secreted IL-1-like activity, and no IL-1 inhibitor was present in the supernatant fluids. In conclusion, muramyl peptides were able to prime PMNs for oxidative burst but not to stimulate IL-1-like factor production.
- Published
- 1987
49. Comparison of immunomodulatory activities in mice and guinea pigs of a synthetic desmuramyl peptidolipid triglymyc
- Author
-
Claude Leclerc, E Lederer, E J Deriaud, Francoise Audibert, N K Masihi, and Louis Chedid
- Subjects
Male ,animal structures ,Ovalbumin ,medicine.medical_treatment ,Guinea Pigs ,Immunology ,Biology ,Pharmacology ,Microbiology ,Guinea pig ,Mice ,Immune system ,Adjuvants, Immunologic ,Antigen ,In vivo ,Tetanus Toxoid ,medicine ,Animals ,Humans ,Lymphocytes ,Mice, Inbred BALB C ,Acetylmuramyl-Alanyl-Isoglutamine ,Antibodies, Bacterial ,Glycopeptide ,carbohydrates (lipids) ,Infectious Diseases ,Mice, Inbred DBA ,Luminescent Measurements ,biology.protein ,bacteria ,Female ,Parasitology ,Adjuvant ,Immunosuppressive Agents ,Research Article - Abstract
A nonpyrogenic desmuramyl peptidolipid, 1-O-(L-alanyl-D-isoglutaminyl-L-alanyl-glycerol-mycolate), had previously been shown to be inactive as adjuvant in guinea pigs, but to be very active in stimulating nonspecific resistance. We now show that 1-O-(L-alanyl-D-isoglutaminyl-L-alanyl-glycerol-mycolate) is capable of enhancing or suppressing the immune responses in mice when injected with or before an antigen. In vivo suppression of the immune response to sheep erythrocytes was also observed with high doses of murabutide, a nonpyrogenic adjuvant-active N-acetylmuramyl-L-alanyl-D-isoglutamine analog. Chemiluminescence measurements with mouse spleen cells show a very strong activity of 1-O-(L-alanyl-D-isoglutaminyl-L-alanyl-glycerol-mycolate) by far superior to the effect obtained with the corresponding muramyl peptide, N-acetylmuramyl-L-alanyl-D-isoglutaminyl-L-alanyl-glycerol-myco late.
- Published
- 1984
50. Past, present and future of the synthetic immunoadjuvant MDP and its analogs
- Author
-
E Lederer and Louis Chedid
- Subjects
Immunosuppression Therapy ,Pharmacology ,Sheep ,Chemical Phenomena ,Chemistry ,Glycopeptides ,Immunity ,Antineoplastic Agents ,Computational biology ,Biochemistry ,Immunoadjuvant ,Mycobacterium ,Adjuvants, Immunologic ,Antibody Formation ,Immunology ,Animals ,Humans ,Emulsions ,Rabbits ,Acetylmuramyl-Alanyl-Isoglutamine - Published
- 1978
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