Monoclonal Anti-Idiotype Vaccine Strategies for Hepatis B Virus

Kennedy, Ronald C.

Abstract

The characterization of idiotypic determinants and the generation of anti-idiotypic reagents have provided powerful tools with which to analyze a given immune response. The idiotype network developed during the course of an immune response provides conceptual insight into the host response to a given antigen. It is proposed to assess the vaccine potential of various monoclonal anti-idiotypic antibody (anti-Id) reagents which result from potential idiotype networks initiated by a host in response to hepatitis B virus (HBV) infection or immunization with hepatitis B surface antigen (HBsAg). Monoclonal anti-Id reagents will be generated against human antibodies to HBsAg (anti-HBs). These anti-Id will be serologically characterized in order to assess whether they are representative of Ab-2 beta internal image or Ab-2 alpha subclasses of anti-Id. The ability of these different classes of anti-Id to modulate the immune response to HbsAg in experimental animals will be examined. The anti-Id induced anti- HBs (Ab-3) responses will be analyzed for idiotype expression. Possible genetic restriction reported in other systems with the Ab-2 alpha classes of anti-Id will be examined in the anti-HBs system using different inbred strains of mice for anti-Id immunization. The potential effects the different classes of monoclonal anti-Id may have on the serological characteristics of an anti-HBs (Ab-3) response will be determined and compared relative to immunization with the nominal antigen (HBsAg). In addition, we will compare the vaccine potential of the various monoclonal anti-Id to that of recombinant HBsAg purified from baculovirus in small experimental animals. Finally, we will examine the idiotype heterogeneity of the human immune response to HBsAg utilizing those monoclonal anti-Id which detect shared anti-HBs idiotypes present in HBV infected and HBsAg vaccinated individuals. The results of this study will provide insight into the vaccine potential of monoclonal anti-Id for preventing HBV infection. Additionally, these studies should provide information concerning whether idiotype networks, expression of particular idiotype, or both are important in the host response to HBV.

Funding Agency

• Agency: National Institute of Health (NIH)
• Institute: National Institute of Allergy and Infectious Diseases (NIAID)
• Type: Research Program Projects (P01)
• Project #: 5P01AI022380-08
• Application #: 3791006
• Support Year: 8
• Fiscal Year: 1992

Institution

• Name: University of Texas Health Science Center San Antonio
• DUNS #: 800772162
• City: San Antonio
• State: TX
• Country: United States
• Zip Code: 78229

Publications

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Lohman, K L; Kieber-Emmons, T; Kennedy, R C (1993) Molecular characterization and structural modeling of immunoglobulin variable regions from murine monoclonal antibodies specific for hepatitis B virus surface antigen. Mol Immunol 30:1295-306

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Magee, D M; Igietseme, J U; Smith, J G et al. (1993) Chlamydia trachomatis pneumonia in the severe combined immunodeficiency (SCID) mouse. Reg Immunol 5:305-11

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Magee, D M; Smith, J G; Bleicker, C A et al. (1992) Chlamydia trachomatis pneumonia induces in vivo production of interleukin-1 and -6. Infect Immun 60:1217-20

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Alderete, J F; Newton, E; Dennis, C et al. (1991) Antibody in sera of patients infected with Trichomonas vaginalis is to trichomonad proteinases. Genitourin Med 67:331-4