Preparation and Formulation of a Human Chorionic Gonadotropin Antifertility Vaccine: Selection of Adjuvant and Vehicle

Authors

  • VERNON C. STEVENS PhD,

    Corresponding author
    1. Division of Reproductive Biology, Department of Obstetrics and Gynecology, The Ohio State University, Columbus
    2. Institute of Immunology, Departments of Medical Genetics, Medical Biophysics, and Clinical Biochemistry, University of Toronto
      Department of Obstetrics and Gynecology, Ohio State University Hospitals, 410 West Tenth Avenue, Columbus, OH 43210.
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  • B. CINADER,

    1. Division of Reproductive Biology, Department of Obstetrics and Gynecology, The Ohio State University, Columbus
    2. Institute of Immunology, Departments of Medical Genetics, Medical Biophysics, and Clinical Biochemistry, University of Toronto
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  • JOHN E. POWELL,

    1. Division of Reproductive Biology, Department of Obstetrics and Gynecology, The Ohio State University, Columbus
    2. Institute of Immunology, Departments of Medical Genetics, Medical Biophysics, and Clinical Biochemistry, University of Toronto
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  • ARTHUR C. LEE,

    1. Division of Reproductive Biology, Department of Obstetrics and Gynecology, The Ohio State University, Columbus
    2. Institute of Immunology, Departments of Medical Genetics, Medical Biophysics, and Clinical Biochemistry, University of Toronto
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  • S. W. KOH

    1. Division of Reproductive Biology, Department of Obstetrics and Gynecology, The Ohio State University, Columbus
    2. Institute of Immunology, Departments of Medical Genetics, Medical Biophysics, and Clinical Biochemistry, University of Toronto
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  • This study received financial support from the Special Programme for Research in Human Reproduction, World Health Organization.

Department of Obstetrics and Gynecology, Ohio State University Hospitals, 410 West Tenth Avenue, Columbus, OH 43210.

Abstract

ABSTRACT: Peptides representing sequences of the beta subunit of HCG (Cys-(Pro)6-111–145 and 109–145) were coupled to tetanus toxoid (TT) and the resultant conjugates used to test the ability of eight experimental adjuvants and six different vehicles for enhancing antibody responses to the peptides in inbred strains of mice (C3H/He, C57BL/6, DBA/1, and SJL) and outbred rabbits. Antibody levels reactive to both 125I-peptides and 125I-HCG were used as criteria of efficacy of these adjuvants and vehicles. In most experiments, groups of animals were immunized with conjugates in complete Freund's adjuvant (CFA) for comparison. Two hydrophilic adjuvants-NAc-nor-Mur-L.ala-D.isoGln, CGP 11,637 and NGlycol-nor-Mur-L.α-abu-D.isoGln, DT-1-were consistently the most effective in stimulating antibody production to both peptides and HCG. An emulsion containing squalene-water stabilized with arlacel A proved to be superior to other vehicles tested for administering conjugates and adjuvants to animals. Antibody levels produced by animals with different genetic backgrounds were shown to be polymorphic with respect to experimental adjuvants, but responses among groups using the same adjuvant and different vehicles were more consistent. Data were obtained suggesting that the coupling of a peptide antigen and a peptide adjuvant to the same carrier holds promise as a model for vaccine development.

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