Cellular correlates of protection have been difficult to standardize due to the complexity of most cell-based immune assays.
The diversity of epitopes targeted by T cells across the human population presents another difficulty for assay development due to HLA allelic variation. Here we will describe T cell receptor (TCR)-based methods for analyzing anti-pathogen immune responses and provide evidence that TCR sequencing is a robust, sensitive, and specific approach for defining relevant immune correlates of protection. The implications for vaccine design and assessment will also be discussed.