Cross-presentation and genome-wide screening reveal candidate T cells antigens for a herpes simplex virus type 1 vaccine
Journal of Clinical Investigation , Volume 122 - Issue 2 p. 654- 673
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 CD137 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.
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|Journal of Clinical Investigation|
|Organisation||Erasmus MC: University Medical Center Rotterdam|
Jing, L, de Haas, J.P, Chong, T.M, Bruckner, J.J, Dann, G.C, Dong, L, … Koelle, D.M. (2012). Cross-presentation and genome-wide screening reveal candidate T cells antigens for a herpes simplex virus type 1 vaccine. Journal of Clinical Investigation, 122(2), 654–673. doi:10.1172/JCI60556