ABSTRACT
INTRODUCTION Most present day phase I/II clinical vaccine trials aim to develop more effective preventive or therapeutic vaccine strategies for infectious diseases and cancer. These studies have at their foundation a comprehensively designed immunologic assay plan that will measure both quantitative and qualitative aspects of the vaccine-induced immune responses. At the same time, they must permit reliable comparisons to the immunogenicities of vaccine strategies that preceded them. During the past 15 years, the field of vaccine research has witnessed an informational and technological explosion that has served to refine vaccine strategies and develop highly complex tools for assessing vaccine immunogenicity and a link to efficacy. Many of these advances have been driven by the critical need to develop an effective AIDS vaccine that could impact on the worldwide epidemic. Although the immunologic ‘‘correlates of protection’’ against HIV infection have yet to be elucidated, most in the scientific community feel that a vaccine is needed that will elicit long-lived and broadly reactive humoral and cellular immune responses, both systemically and mucosally. For the currently licensed human vaccines in use today, the role of vaccine-induced T-cell responses in preventing infections or disease has been less well established than the role of neutralizing antibodies, although in many instances the basis for protection by these vaccines has never been clearly delineated.
CHALLENGES ASSOCIATED WITH MEASURING VACCINE-INDUCED T-CELL RESPONSES Since most developmental vaccine strategies are built upon the concept of making incremental improvements on existing vaccines, the assays used in assessing immunogenicity must provide reliable comparative data. This aspect of vaccine testing demands that highly standardized and formally validated assays be used in providing immunologic end points. The assessment of vaccine-induced T-cell responses in the setting of phase I/II clinical trials presents formidable challenges that do not apply to routine serologic immunogenicity testing, although standardization of the latter is of equal importance. All too often, optimization and standardization efforts are focused on the sophisticated technologies used to measure antigen-specific T-cell responses, with very little attention paid to an important aspect of immunogenicity testing, the overall functional integrity of the clinical specimens, in most
