Systematic analysis of T cell responses specific to the Epstein-Barr virus proteome using ATLAS (TM)

Abstract Epstein-Barr virus (EBV) is a human herpesvirus infecting 95% of the world population. Primary infection can cause acute infectious mononucleosis (AIM), mainly when EBV is acquired later in life. In addition, EBV establishes latency and has been associated with several cancers. To date, efforts to develop vaccines for prevention of infection or disease by induction of gp350-specific neutralizing antibody responses have failed. To improve antigen selection for future vaccines, we utilized ATLAS™, a screening platform that can characterize the specificity of CD4+ and CD8+ T cell recall responses to the entire EBV proteome without bias of immunodominance. Firstly, we measured antigen-specific T cell activation in 15 AIM patients longitudinally during and 6 weeks after the symptomatic disease phase. For both T cell subsets, the breadth of response significantly decreased with resolution of disease, likely in parallel to the contraction of the CD8+ T cell compartment associated with AIM clearance. Notably, we detected a substantial overlap in antigen specificity between T cell responses in samples collected during AIM and in convalescence. Secondly, we identified EBV antigens that elicit T cell responses in both seropositive and seronegative but possibly exposed adolescents. Interim analysis revealed that ATLAS™ not only confirmed several previously described CD4+ and CD8+ T cell targets in latently infected individuals, but also identified novel T cell antigens independently of serostatus. Ongoing comparative analyses will focus on differences in the memory T cell repertoire between cohorts and on antigens overrepresented in exposed seronegative individuals that may be protective and therefore of value for vaccine development.