T cell analysis in vaccination

A major problem in the analysis of vaccine candidates is the lack of any agreed upon surrogates of efficacy, which means that for diseases that depend on a strong T cell response (HIV, TB especially) the only option is to perform an efficacy trial, involving thousands of subjects, enormous costs, and years before the results are known [1]. We also know that T cell responses are an important part of most pathogen responses, and so identifying key T cell response metrics in early vaccine trials would be generally useful. Given our ignorance of what the most important variables are, what would we like to measure and how can this be accomplished, especially given the explosion of new technologies that are available? What follows is a consideration of what should be measured, with the caveat that some of these will be more important than others.