Successful Immunization with a Totally Synthetic Diphtheria Vaccine

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1982 Aug 1

PMID 6956913

Citations 23

Authors

F Audibert

M Jolivet

L CHEDID

R Arnon

M Sela

Affiliations

Soon will be listed here.

Abstract

Three peptides corresponding to fragments of diphtheria toxin have been synthesized. They include the previously described tetradecapeptide and two structural analogs, the hexadecapeptide and the octadecapeptide. Conjugates of these peptides to proteins or a synthetic carrier have induced in guinea pig protection against the dermonecrotic activity of diphtheria toxin. All of the conjugates were immunogenic when administered either in complete Freund's adjuvant or with N-acetylmuramyl-L-alanyl-D-isoglutamine in aqueous medium. Positive immune response toward the octadecapeptide was obtained in mice as well. In this case, the immunogenic combinations were conjugates with bovine serum albumin administered either in Freund's adjuvant or with the muramyl dipeptide and a complete synthetic conjugate comprising both the octadecapeptide and the muramyl dipeptide covalently attached to a synthetic carrier, multichain poly(DLAla). This last immunogen, which induced the most effective immune response, is a completely synthetic immunogen with built-in adjuvanticity and induces protective antitoxic immunity when administered in a physiological medium.

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References

Sela M . Antigenicity: some molecular aspects. Science. 1969; 166(3911):1365-74. DOI: 10.1126/science.166.3911.1365. View

Arnon R, Maron E, Sela M, ANFINSEN C . Antibodies reactive with native lysozyme elicited by a completely synthetic antigen. Proc Natl Acad Sci U S A. 1971; 68(7):1450-5. PMC: 389215. DOI: 10.1073/pnas.68.7.1450. View

Ellouz F, Adam A, Ciorbaru R, Lederer E . Minimal structural requirements for adjuvant activity of bacterial peptidoglycan derivatives. Biochem Biophys Res Commun. 1974; 59(4):1317-25. DOI: 10.1016/0006-291x(74)90458-6. View

Collier R . Diphtheria toxin: mode of action and structure. Bacteriol Rev. 1975; 39(1):54-85. PMC: 413884. DOI: 10.1128/br.39.1.54-85.1975. View

Kotani S, Watanabe Y, Shimono T, Narita T, Kato K . Immunoadjuvant activities of cell walls, their water-soluble fractions and peptidoglycan subunits, prepared from various gram-positive bacteria, and of synthetic n-acetylmuramyl peptides. Z Immunitatsforsch Exp Klin Immunol. 1975; 149(2-4):302-19. View

Merser C, Sinay P, Adam A . Total synthesis and adjuvant activity of bacterial peptidoglycan derivatives. Biochem Biophys Res Commun. 1975; 66(4):1316-22. DOI: 10.1016/0006-291x(75)90503-3. View

Audibert F, CHEDID L, Lefrancier P, CHOAY J . Distinctive adjuvanticity of synthetic analogs of mycobacterial water-soluble components. Cell Immunol. 1976; 21(2):243-9. DOI: 10.1016/0008-8749(76)90053-8. View

Langbeheim H, Arnon R, Sela M . Antiviral effect on MS-2 coliphage obtained with a synthetic antigen. Proc Natl Acad Sci U S A. 1976; 73(12):4636-40. PMC: 431576. DOI: 10.1073/pnas.73.12.4636. View

PAPPENHEIMER Jr A . Diphtheria toxin. Annu Rev Biochem. 1977; 46:69-94. DOI: 10.1146/annurev.bi.46.070177.000441. View

10.

Audibert F, CHEDID L, Hannoun C . [Enhancement of the immune response to influenza vaccine by a synthetic glycopeptide adjuvant (N-acetyl muramy1-L-analyl-D-isoglutamine)]. C R Acad Hebd Seances Acad Sci D. 1977; 285(4):467-70. View

11.

Webster R, Glezen W, Hannoun C, Laver W . Potentiation of the immune response to influenza virus subunit vaccines. J Immunol. 1977; 119(6):2073-7. View

12.

Siddiqui W, Taylor D, Kan S, Kramer K, Kotani S, Shiba T . Vaccination of experimental monkeys against Plasmodium falciparum: a possible safe adjuvant. Science. 1978; 201(4362):1237-9. DOI: 10.1126/science.99814. View

13.

Goodfriend T, Levine L, Fasman G . ANTIBODIES TO BRADYKININ AND ANGIOTENSIN: A USE OF CARBODIIMIDES IN IMMUNOLOGY. Science. 1964; 144(3624):1344-6. DOI: 10.1126/science.144.3624.1344. View

14.

Langbeheim H, Arnon R, Sela M . Adjuvant effect of a peptidoglycan attached covalently to a synthetic antigen provoking anti-phage antibodies. Immunology. 1978; 35(4):573-9. PMC: 1457369. View

15.

CHEDID L, Audibert F, Johnson A . Biological activities of muramyl dipeptide, a synthetic glycopeptide analogous to bacterial immunoregulating agents. Prog Allergy. 1978; 25:63-105. View

16.

REESE R, TRAGER W, Jensen J, Miller D, Tantravahi R . Immunization against malaria with antigen from Plasmodium falciparum cultivated in vitro. Proc Natl Acad Sci U S A. 1978; 75(11):5665-8. PMC: 393028. DOI: 10.1073/pnas.75.11.5665. View

17.

CHEDID L, Parant M, Parant F, Audibert F, Lefrancier F, CHOAY J . Enhancement of certain biological activities of muramyl dipeptide derivatives after conjugation to a multi-poly(DL-alanine)--poly(L-lysine) carrier. Proc Natl Acad Sci U S A. 1979; 76(12):6557-61. PMC: 411905. DOI: 10.1073/pnas.76.12.6557. View

18.

Mozes E, Sela M, CHEDID L . 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). Proc Natl Acad Sci U S A. 1980; 77(8):4933-7. PMC: 349963. DOI: 10.1073/pnas.77.8.4933. View

19.

Arnon R . Chemically defined antiviral vaccines. Annu Rev Microbiol. 1980; 34:593-618. DOI: 10.1146/annurev.mi.34.100180.003113. View

20.

Woodard L, Toone N, McLaughlin C . Immunogenic properties of soluble antigens or whole cells of Brucella abortus strain 45/20 associated with immunoadjuvants. I. Soluble antigens. Can J Comp Med. 1980; 44(4):453-5. PMC: 1320104. View