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Immunopharmacological study of CCA (lobenzarit disodium), an anti-arthritis agent
397
IMMUNOPHARMACOLOGICAL STUDY OF CCA(LOBENZARIT DISODIUM),AN ANTI-ARTHRITIS AGENT Masao Fujimoto,Isamu Sugwara,Makoto Kimoto,Shigeaki Ishizaka and Tadasu Tsujii Third Dept. of Int. Med.,Nara Medical University,Nara 634,Japan
28
In vitro effects of CCA,an anti-arthritis agent, were studied upon autologous mixed lymphocyte reaction(AMLR),lymphocyte mitogenesis,IL 1 and IL 2 production,immunoglobulin ( IgM and IgG) production and~--interferon(IFN) production. CCA at 507~g/ml,which was not toxic to cells,blocked AMLR,IL 1 production and immunoglobulin production significantly, while CCA at the same dose did not affect IL 2 production and lymphocyte mitogenic responses to Staphylococcus aureus Cowan I(SAC) and pokeweed mitogen(PWM). CCA at both 20ng/ml and 20jug/ml induced human]f-IFN. Addition of IL 1 and/or IL 2 reversed inhibitory effect of CCA on AMLR. These data suggest that CCA exerts its actions by mainly affecting T cells and monocytes and can be used as an immunomodulating agent.
NOVEL VACCINES
BORDETELLA PERTUSSIS COMPONENTSGIVEN WITH CARRIER PRIMING CAN OVERCOMEEPITOPE SUPPRESSION IN SYNTHETIC VACCINE MODELS. M.P. Schutze, F.R. Vogel, C. Leclerc, F. Audibert, M. J o l i v e t and L. Chedid. Immunoth~rapie Exp~rimentale, I n s t i t u t Pasteur, Paris, France.
31
The induction of an immune response against synthetic peptides usually requires the use of an immunogenic c a r r i e r . The use of tetanus toxoid (TT) has been proposed f o r t h i s purpose as i t is h i g h l y immunogenic and has been used extensively in humans. Previous studies have demonstrated that an epitope s p e c i f i c suppression of IgG antibody responses occurs when mice previously primed with a c a r r i e r are subsequently immunized with a haptenic epitope linked to the same c a r r i e r . The same studies have shown that B.pertussis vaccine administered with the c a r r i e r abrogates epitope suppression. In the present study, epitope suppression was studied using as epitopes two synthetic peptide vaccines, containing a TT c a r r i e r . Our results demonstrate that : i ) mice primed with TT one month before immunization with peptide-TT conjugates e x h i b i t e d an enhanced secondary anti-TT response but decreased anti -pepti de responses as compared to antibody t i t e r s of mice which had not been primed with TT; 2) B.pertussis vaccine, or i t s p u r i f i e d components, t o x i n and endotoxin, can avert epitope suppression i f administered at the time of c a r r i e r priming. Enhanced antibody responses, as compared to those of unprimed animals, against both the c a r r i e r and the s y n t h e t i c peptides were observed when B.pertussis components were given with the c a r r i e r . ABILITY OF A SYNTHETIC STREPTOCOCCALPEPTIDE TO ELICIT IMMUNOLOGICALMEMORYIN THE ABSENCE OF DETECTABLE ANTIBODY PRODUCTION. O. Abehsira-Amar+, M. J o l i v e t +, F. Audibert +, H. Gras-Masse °, A. Tartar ° , E.H. Beaches and L. Chedid +. +C.N.R.S. 04-0579, Immunoth~rapie Exp6rimentale, I n s t i t u t Pasteur, Paris, France. °Facult~ de Pharmacie, L i l l e , France. +Veterans Administration, Memphis, U.S.A. A s y n t h e t i c peptide S-CB7 ( s y n t h e t i c cyanogen bromide fragment 7) reproducing a sequence of 34 amino acid long of a membrane protein from Streptococcus pyogenes type 24 (M24 protein) has been injected in a polymeric form (poly S-CB7) to mice in phosphate buffered saline (PBS) with or w i t h o u t the s y n t h e t i c adjuvant, Murabutide. This i n j e c t i o n was followed by a secondary immunization by a non-immunogenic dose of M24 protein also in PBS. Anti-S-CB7 and a n t i - p r o t e i n M24 antibodies were t i t r a t e d in the sera by the ELISA method. In the absence of adjuvant no antibodies were produced a f t e r the f i r s t or the second i n j e c t i o n . In contrast, although i t did not induce detectable amounts of antibodies, this polymer given with Murabutide could however potentiate the antibody response to a subsequent challenge with a non-immunogenic dose of M24 protein. Most of the antibodies produced were directed toward S-CB7 determinant(s) and recognized the M24 protein. The experiments demonstrate that peptides can stimulate immunological memory, independently of t h e i r capacity to induce detectable amounts of c i r c u l a t i n g antibodies.
32
IMMUNOPHARMACOLOGICAL STUDY OF CCA(LOBENZARIT DISODIUM),AN ANTI-ARTHRITIS AGENT Masao Fujimoto,Isamu Sugwara,Makoto Kimoto,Shigeaki Ishizaka and Tadasu Tsujii Third Dept. of Int. Med.,Nara Medical University,Nara 634,Japan
28
In vitro effects of CCA,an anti-arthritis agent, were studied upon autologous mixed lymphocyte reaction(AMLR),lymphocyte mitogenesis,IL 1 and IL 2 production,immunoglobulin ( IgM and IgG) production and~--interferon(IFN) production. CCA at 507~g/ml,which was not toxic to cells,blocked AMLR,IL 1 production and immunoglobulin production significantly, while CCA at the same dose did not affect IL 2 production and lymphocyte mitogenic responses to Staphylococcus aureus Cowan I(SAC) and pokeweed mitogen(PWM). CCA at both 20ng/ml and 20jug/ml induced human]f-IFN. Addition of IL 1 and/or IL 2 reversed inhibitory effect of CCA on AMLR. These data suggest that CCA exerts its actions by mainly affecting T cells and monocytes and can be used as an immunomodulating agent.
NOVEL VACCINES
BORDETELLA PERTUSSIS COMPONENTSGIVEN WITH CARRIER PRIMING CAN OVERCOMEEPITOPE SUPPRESSION IN SYNTHETIC VACCINE MODELS. M.P. Schutze, F.R. Vogel, C. Leclerc, F. Audibert, M. J o l i v e t and L. Chedid. Immunoth~rapie Exp~rimentale, I n s t i t u t Pasteur, Paris, France.
31
The induction of an immune response against synthetic peptides usually requires the use of an immunogenic c a r r i e r . The use of tetanus toxoid (TT) has been proposed f o r t h i s purpose as i t is h i g h l y immunogenic and has been used extensively in humans. Previous studies have demonstrated that an epitope s p e c i f i c suppression of IgG antibody responses occurs when mice previously primed with a c a r r i e r are subsequently immunized with a haptenic epitope linked to the same c a r r i e r . The same studies have shown that B.pertussis vaccine administered with the c a r r i e r abrogates epitope suppression. In the present study, epitope suppression was studied using as epitopes two synthetic peptide vaccines, containing a TT c a r r i e r . Our results demonstrate that : i ) mice primed with TT one month before immunization with peptide-TT conjugates e x h i b i t e d an enhanced secondary anti-TT response but decreased anti -pepti de responses as compared to antibody t i t e r s of mice which had not been primed with TT; 2) B.pertussis vaccine, or i t s p u r i f i e d components, t o x i n and endotoxin, can avert epitope suppression i f administered at the time of c a r r i e r priming. Enhanced antibody responses, as compared to those of unprimed animals, against both the c a r r i e r and the s y n t h e t i c peptides were observed when B.pertussis components were given with the c a r r i e r . ABILITY OF A SYNTHETIC STREPTOCOCCALPEPTIDE TO ELICIT IMMUNOLOGICALMEMORYIN THE ABSENCE OF DETECTABLE ANTIBODY PRODUCTION. O. Abehsira-Amar+, M. J o l i v e t +, F. Audibert +, H. Gras-Masse °, A. Tartar ° , E.H. Beaches and L. Chedid +. +C.N.R.S. 04-0579, Immunoth~rapie Exp6rimentale, I n s t i t u t Pasteur, Paris, France. °Facult~ de Pharmacie, L i l l e , France. +Veterans Administration, Memphis, U.S.A. A s y n t h e t i c peptide S-CB7 ( s y n t h e t i c cyanogen bromide fragment 7) reproducing a sequence of 34 amino acid long of a membrane protein from Streptococcus pyogenes type 24 (M24 protein) has been injected in a polymeric form (poly S-CB7) to mice in phosphate buffered saline (PBS) with or w i t h o u t the s y n t h e t i c adjuvant, Murabutide. This i n j e c t i o n was followed by a secondary immunization by a non-immunogenic dose of M24 protein also in PBS. Anti-S-CB7 and a n t i - p r o t e i n M24 antibodies were t i t r a t e d in the sera by the ELISA method. In the absence of adjuvant no antibodies were produced a f t e r the f i r s t or the second i n j e c t i o n . In contrast, although i t did not induce detectable amounts of antibodies, this polymer given with Murabutide could however potentiate the antibody response to a subsequent challenge with a non-immunogenic dose of M24 protein. Most of the antibodies produced were directed toward S-CB7 determinant(s) and recognized the M24 protein. The experiments demonstrate that peptides can stimulate immunological memory, independently of t h e i r capacity to induce detectable amounts of c i r c u l a t i n g antibodies.
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