ANTIBODIES AS A MARKER OF EFFECTIVE IMMUNIZATION

University Of Washington, Seattle WA

Investigators

Linked publications & trials

Abstract

Description: (provided by applicant) The assessment of antibody immunity may be a useful tool in defining an immunologic surrogate for vaccine efficacy. In some infectious disease models, total levels of antigen specific antibodies predict protection. In fact, in some cases the development of antibody immunity is considered a surrogate for the generation of a T cell response. Techniques are available that will allow rapid and highly quantitative assessment of not only the total amount and class of antigen specific antibody elicited after immunization, but also the isotype of antibody, and an assessment of antibody-antigen avidity as an estimate of function. Evaluation of multiple parameters of antibody immunity , in both foreign antigen and tumor antigen systems, will establish a template for the detailed analysis of antibody immunity generated during cancer vaccine human clinical trials. The generation of antibody immunity has been assessed in cancer vaccine trials. Total quantitative IgG and IgM has been evaluated in a variety of tumor antigen systems after immunization. There is some suggestion, in these early phase studies, that the generation of antibody immunity to tumors may have a clinical effect and correlate to tumor regression or time to relapse in melanoma models. Currently larger clinical trials have been planned or are in process to determine clinical efficacy of immunization strategies such as melanoma cell vaccines or anti-idiotype vaccines designed to elicit antibody immunity. The clinical finding, that measurable immunity can be generated in patients with cancer by active immunization with a cancer vaccine and some early indication that this immunity may have a clinical effect sets the stage for the development of highly reproducible clinical grade assays to establish an immunologic correlate of vaccine efficacy. The specific aims of this proposal are to: (1) determine whether quantitative assessment of class antibody response and isotype of IgG from the sera of volunteer donors and cancer patients, can predict the T cell response to foreign protein antigens, (2) determine whether quantitative assessment of class antibody response and isotype of IgG from the sera of volunteer donors and cancer patients, can predict the T cell response to tumor antigens, (3) assess antibody avidity to foreign proteins and tumor antigens and determine whether antibody avidity correlates to a particular isotype or specific T cell response, ( 4) evaluate the quantitative tumor antigen specific antibody response and avidity as potential surrogates of immune protection and immunization efficacy in vaccination of CEA and neu transgenic mice, (5) determine whether the magnitude, class, isotype, or avidity of an antibody response can predict immunization to cancer antigens and whether levels achieved are that similar to infectious disease or foreign antigens in human clinical trials of CEA, HER2, gp 100, and MAGE3 vaccines.