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Cross-presentation and genome-wide screening reveal candidate T cells antigens for a herpes simplex virus type 1 vaccine.
Title | Cross-presentation and genome-wide screening reveal candidate T cells antigens for a herpes simplex virus type 1 vaccine. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Jing, L, Haas, J, Chong, TM, Bruckner, JJ, Dann, GC, Dong, L, Marshak, JO, McClurkan, CL, Yamamoto, TN, Bailer, SM, Laing, KJ, Wald, A, Verjans, GM, Koelle, DM |
Journal | J Clin Invest |
Volume | 122 |
Issue | 2 |
Pagination | 654-73 |
Date Published | 2012 Feb 1 |
ISSN | 1558-8238 |
Keywords | Adult, Antigens, CD137, Antigens, Viral, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cells, Cultured, Cross-Priming, Cytotoxicity, Immunologic, Female, Herpes Simplex, Herpesvirus 1, Human, HLA Antigens, Humans, Interferon-gamma, Male, Middle Aged, Viral Vaccines, Young Adult |
Abstract | 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. |
DOI | 10.1172/JCI60556 |
Alternate Journal | J. Clin. Invest. |
PubMed ID | 22214845 |