Cross-presentation and genome-wide screening reveal candidate T cells antigens for a herpes simplex virus type 1 vaccine

LC Jing, J Haas, TM Chong, JJ Bruckner, GC Dann, LC Dong, JO Marshak, CL McClurkan, TN Yamamoto, SM Bailer, KJ Laing, A Wald, Georges Verjans, DM Koelle

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Herpes simplex virus type 1 (HSV-1) not only causes painful recurrent oral-labial infections, it can also cause permanent brain damage and blindness. There is currently no HSV-1 vaccine. An effective vaccine must stimulate coordinated T cell responses, but the large size of the genome and the low frequency of HSV-1-specific T cells have hampered the search for the most effective T cell antigens for inclusion in a candidate vaccine. We have now developed what we believe to be novel methods to efficiently generate a genome-wide map of the responsiveness of HSV-1-specific T cells, and demonstrate the applicability of these methods to a second complex microbe, vaccinia virus. We used cross-presentation and CD 137 activation-based FACS to enrich for polyclonal CD8(+) T effector T cells. The HSV-1 proteome was prepared in a flexible format for analyzing both CD8(+) and CD4(+) T cells from study participants. Scans with participant-specific panels of artificial APCs identified an oligospecific response in each individual. Parallel CD137-based CD4(+) T cell research showed discrete oligospecific recognition of HSV-1 antigens. Unexpectedly, the two HSV-1 proteins not previously considered as vaccine candidates elicited both CD8(+) and CD4(+) T cell responses in most HSV-1-infected individuals. In this era of microbial genomics, our methods also - demonstrated in principle for vaccinia virus for both CD8(+) and CD4(+) T cells - should be broadly applicable to the selection of T cell antigens for inclusion in candidate vaccines for many pathogens.
Original languageUndefined/Unknown
Pages (from-to)654-673
Number of pages20
JournalJournal of Clinical Investigation
Issue number2
Publication statusPublished - 2012

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