The aim of this proposal is to evaluate the utility of monoclonal antiidiotypic antibodies which mimic the a determinant of hepatitis B surface antigen (HBsAG) to overcome some of the limitations of conventional vaccines (HBsAg, recombinant and peptide). One of the shortcomings of the currently licensed hepatitis B vaccine is that a small group of individuals who receive the vaccine (including immunocompromised patients) fail to make an anti-HBs response. The question that this proposal wishes to address is, can an anti-idiotype vaccine overcome this non- responsiveness? It is very likely, that this group of non- responders to the vaccine will also be unable to mount an immune response on exposure to the hepatitis B virus (HBV) itself. These individuals will become chronic carriers of the disease, with the possibility of having hepatocellular carcinoma later in life, as there is good evidence showing the increased incidence of this form of cancer subsequent to HBV infection. It had been previously established, that in mice there is a distinct H-2 restricted hierarchy of responsiveness to HBsAg. It is our objective, using a well0-defined animal model to examine the ability of a monoclonal anti-idiotype vaccine to overcome the non-responsiveness seen against the nominal antigen in both human and murine species. Of particular importance will be the results from immunization of outbred mice whose response should be very relevant to the clincical situation. In addition, the use of a tolerant mouse model will allow us to examine the ability of the anti-id vaccine to break tolerance, probably through the expression of otherwise silent clones. Based on previous experience with idiotype vaccines in this laboratory, we will use conjugates of hepatitis B surface antigen imaging Ab2beta (with potent carriers) as vaccines. Such carrier-2b2beta conjugates have the ability to present an antigenic determinant in an different molecular environment, i.e. an antigenic epitope is mimicked in the context of an immunoglobulin structure.
| Pride, M W; Thakur, A; Thanavala, Y (1993) Mimicry of the a determinant of hepatitis B surface antigen by an antiidiotypic antibody. I. Evaluation in hepatitis B surface antigen responder and nonresponder strains. J Exp Med 177:127-34 |
| Pride, M W; Shi, H; Anchin, J M et al. (1992) Molecular mimicry of hepatitis B surface antigen by an anti-idiotype-derived synthetic peptide. Proc Natl Acad Sci U S A 89:11900-4 |
