Cross-presentation and genome-wide screening reveal candidate T cells antigens for a herpes simplex virus type 1 vaccine.
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.
Department of Medicine, University of Washington, Seattle, Washington, USA.
Lichen
L
Jing
Jürgen
J
Haas
Tiana M
TM
Chong
Joseph J
JJ
Bruckner
Greg C
GC
Dann
Lichun
L
Dong
Joshua O
JO
Marshak
Christopher L
CL
McClurkan
Tori N
TN
Yamamoto
Susanne M
SM
Bailer
Kerry J
KJ
Laing
Anna
A
Wald
Georges M G M
GM
Verjans
David M
DM
Koelle
D000328:Adult; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002478:Cells, Cultured; D045142:Cross-Priming / Q000276:immunology*; D003602:Cytotoxicity, Immunologic / Q000276:immunology; D005260:Female; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006561:Herpes Simplex / Q000517:prevention & control; D018259:Herpesvirus 1, Human / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D008297:Male; D008875:Middle Aged; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9 / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*; D055815:Young Adult
D000956:Antigens, Viral; D006680:HLA Antigens; D053261:Tumor Necrosis Factor Receptor Superfamily, Member 9; D014765:Viral Vaccines; D007371:Interferon-gamma