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M Jolivet

Publications and source records attributed to M Jolivet.

12 recordsLinked to original sources
PubMed1990

Polyvalent synthetic vaccines: relationship between T epitopes and immunogenicity.

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 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 A similar immune response was obtained with a second polyvalent vaccine where the P. knowlesi peptide had been replaced by the P. falciparum peptide.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.

Amino Acid Sequence↗
PubMed1990

Fibroblast growth factor (FGF) and an FGF-like molecule in pituitary extracts stimulate thymic epithelial cell proliferation.

A bovine pituitary extract (BPE) induces thymidine incorporation into human thymic epithelial cells (TEC) in vitro. Previous data demonstrated that its effects resulted in epithelial cell replication and suggested that the active component of BPE was likely to be a growth factor, different from epidermal growth factor (EGF) and interleukin 1 (IL1). In this report we present evidence to identify the active component of BPE as a fibroblast growth factor (FGF) family member, based upon several criteria: a) Purified bovine and human recombinant FGF also enhanced TEC proliferation in vitro. b) Neutralization studies showed antigenic similarities between BPE and basic FGF. c) Biochemical analytical studies allowed purification of BPE by its affinity for heparin with elution at 3M NaCl, and gel filtration sizing yielded a 73 KD molecule with which basic FGF co-eluted. The isoelectric point was found to be between 6.3 and 6.6 and this is the only finding not consistent with the characterization of basic FGF as the factor responsible for the activity of BPE on TEC proliferation.

Ammonium Sulfate↗
PubMed1987

Modulation of carrier-induced epitopic suppression by Bordetella pertussis components and muramyl peptide.

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.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1987

A potential anti-pregnancy vaccine built by conjugation of the beta-subunit of human chorionic gonadotropin to adjuvant-active muramyl peptide.

The beta-subunit of human chorionic gonadotropin (hCG) conjugated to tetanus toxoid is being investigated as a vaccine for human fertility control. Initial clinical trials indicated that the level of antibody response induced by such an immunogen was not always sufficient to prevent pregnancy. Therefore, efforts are being made to evaluate new carriers for the beta-subunit and to select adjuvants to yield a more efficient vaccine. In the present report, we demonstrate that conjugates of the beta-subunit of hCG with muramyl dipeptide (MDP), or its nonpyrogenic derivative murabutide, may have potential as an effective antipregnancy vaccine. The copolymer of beta hCG and MDP administered with Al(OH)3 to mice induced a high anti-beta hCG response, better than that induced by the conjugate of beta hCG to tetanus toxoid given with Al(OH)3. Moreover, the antibodies induced by such an immunogen were competent for neutralizing the biological activity of hCG in vivo. Even more interesting, a copolymer of beta hCG and of murabutide induced high levels of biologically active antibodies. This immunogen may represent a promising candidate for the development of an efficient vaccine for human fertility control.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1987

Enhanced epitopic response to a synthetic human malarial peptide by preimmunization with tetanus toxoid carrier.

Successful human vaccination by synthetic malarial sporozoite peptides may depend on the choice of an appropriate carrier. Tetanus toxoid (TT) has been proposed because of its safe and widespread use in humans. Paradoxically, however, prior exposure to this toxoid vaccine could produce specific epitopic suppression against synthetic malarial peptides conjugated to this same protein as carrier. Indeed, we have previously reported that such a phenomenon can occur in the case of a synthetic vaccine made with a streptococcal peptide conjugated to TT. Our present study shows that similar results can be observed in mice preimmunized with TT 1 month before the administration of a conjugate containing TT and a Plasmodium knowlesi peptide. Analysis of the isotypic pattern of the antipeptide response showed that the immunoglobulin G1 (IgG1) subclass and especially the IgG2a and IgG2b subclasses were suppressed. In contrast, when a sporozoite peptide from Plasmodium falciparum was coupled to TT, the total antipeptide antibodies and particularly the IgG1 subclass were enhanced by preimmunization by TT. This increase of antipeptide antibodies was correlated with a greater ability of the sera to neutralize sporozoite infectivity. These results indicate that prior exposure to TT does not systematically impair the antibody response against a peptide administered as a peptide-TT conjugate.

Adjuvants, Immunologic↗
PubMed1987

Monoclonal B-cell response to diphtheria toxoid: evidence for cross-reactive epitopes.

Our previous studies on the human specific B- and T-cell responses against diphtheria toxoid (DT) had shown that the B- and T-cell antigenic determinants were mostly assembled topographic sites with large intra-molecular cross-reactivities. In order to characterize further the B-cell responses against DT, and to investigate these cross-reactivities, we have produced 54 murine monoclonal antibodies (moAbs) against the native DT. Determination of their antigenic specificity showed that 25 moAbs recognized conformational determinants on the native DT, 20 moAbs reacted against the A fragment (DTA) of the toxin, and nine moAbs reacted with at least three distinct highly purified CNBr peptides of the B fragment (DTB); some of them simultaneously recognized two or three purified CNBr peptides of DTB. As shown by cross-inhibition studies, the epitopes cross-reacting with those moAbs were distinct. Previously described sequence data indicated that these epitopes were not induced by repetitive amino-acid sequences. Finally, a cross-reactive idiotype was shared by moAbs specific for the CB1 and the CB3 peptides of DTB. Altogether, these data indicate that anti-DT moAbs are mostly directed against conformational determinants, and may cross-react with several DTB CNBr peptides.

Animals↗
PubMed1985

Carrier-induced epitopic suppression, a major issue for future synthetic vaccines.

Synthetic antigens have been shown, in experimental models, to induce protective immunity against a variety of pathogens. These studies have demonstrated that, due to their low immunogenicity, these synthetic antigens required conjugation to carrier molecules. Therefore, the choice of appropriate carriers for human immunization by future synthetic vaccines is a major issue. Tetanus toxoid is generally considered to be an effective potential carrier devoid of side-effects. However, the present study performed in mice with two synthetic vaccine models demonstrates that the immune response against the synthetic epitopes conjugated to tetanus toxoid can be suppressed by pre-existing immunity against this same carrier. Because most humans have been exposed to this antigen, this effect may have important implications for the development of synthetic vaccines.

Animals↗
PubMed1985

Identification of epitopes associated with hCG and the beta hCG carboxyl terminus by monoclonal antibodies produced against a synthetic peptide.

We have produced a library of monoclonal antibodies directed against a 37-amino acid synthetic polypeptide analogous to the carboxyl terminus of hCG. Five antibodies, designated FB01, FB02, FB03, FB04, and FB00, were developed and analyzed with respect to affinity and specificity for epitopes on human chorionic gonadotropin (hCG) and beta hCG by enzyme-linked immunoabsorbent and radioimmunoassays (RIA). All monoclonal antibodies demonstrated low affinity constants (approximately 10(-7) liters/mol) compared with those obtained by immunization with native beta hCG. One antibody, namely FB00, bound only to the synthetic peptide, whereas all other monoclonal antibodies recognized either free native beta hCG or both beta hCG and HCG. Antibodies produced against the synthetic peptide did not cross-react with other glycoprotein hormones such as LH, TSH, and FSH. Characterization of the monoclonal antibody-binding sites revealed the presence of at least four separate and distinct epitopes on the last 35 amino acids of beta hCG. Indeed, one epitope recognized by FB01 is located between residues 109 and 118, whereas another antigenic region recognized by FB04 appears to be present on the 109-121 portion of the molecule near or at position 118. One additional antigenic site was localized between residues 118 and 136. Finally, FB00 recognized an epitope located on the last 10 amino acids (136-145) of beta hCG. With the use of such antibodies, two- and three-site monoclonal RIA were developed and employed to detect free beta hCG and hCG in sera of patients with choriocarcinoma. These assays may be useful in the detection of beta hCG- and hCG-producing tumors and subsequent monitoring of patients in response to surgery and/or chemotherapy.

Amino Acid Sequence↗
PubMed1975

(-)-(minus)

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Bacillus megaterium↗
PubMed1975

[Chemically controlled depolymerization of beta hydroxybutyric lipids (PHB) in Bacillus megaterium. Isolation and structure of the oligomers of D(-)beta hydroxybutyric acid].

Partial depolymerisation of PHB by chemical means to the appearance of homologous polymers from PHB constituted of short carbon chains and oligomers which represent the first elements of this macromolecule. The chemical structure of these oligomers ranging from dimer to heptamer has been essentially deduced from their mass spectrum and then confirmed by studying their physical, chemical and biological properties.

Bacillus megaterium↗
PubMedDate not supplied

Role of the proline residues on the immunogenic properties of a P. falciparum circumsporozoite peptide linked to a carrier protein.

The circumsporozoite (CS) protein of P. falciparum contains an immunodominant epitope, NADP, that is repeated 37 times in the native molecule. The presence of proline in the coat proteins of the Plasmodium parasite at various developmental stages and strains is a frequent occurrence. In this study we evaluate the influence of substitution of proline residues by glycine on the immunogenic behavior of two tandemly repeated peptides linked via glutaraldehyde to a protein carrier: The (NANP)4 P. falciparum circumsporozoite peptide and its glycine-substitute analog, (NANG)4. The results obtained show that the (NANP)4 induces antibodies which recognize the peptide free in solution, bound on a solid phase, and linked to a carrier protein. It has been previously reported that such antibodies recognize the antigenic sites of the peptide in the native protein on the surface of the sporozoite. Antibodies raised against (NANG)4 in the same experimental conditions as (NANP)4, cannot recognize the peptide free in solution or bound to the solid phase. However, these antibodies can react with the peptide when it is linked to a protein carrier. The coupling of a glycine-containing analog to a carrier results in a significant shift in its conformation, allowing it to be recognized by the antibodies.

Animals↗