Cross-presentation and genome-wide screening reveal candidate T cells antigens for a herpes simplex virus type 1 vaccine
Lichen Jing, … , Georges M.G.M. Verjans, David M. Koelle
Lichen Jing, … , Georges M.G.M. Verjans, David M. Koelle
Published January 3, 2012
Citation Information: J Clin Invest. 2012;122(2):654-673. https://doi.org/10.1172/JCI60556.
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Technical Advance Infectious disease

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

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.

Authors

Lichen Jing, Jürgen Haas, Tiana M. Chong, Joseph J. Bruckner, Greg C. Dann, Lichun Dong, Joshua O. Marshak, Christopher L. McClurkan, Tori N. Yamamoto, Susanne M. Bailer, Kerry J. Laing, Anna Wald, Georges M.G.M. Verjans, David M. Koelle

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Figure 7

Graphical summary of direct PBMC IFN-γ ELISPOT.

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Graphical summary of direct PBMC IFN-γ ELISPOT. HSV-1 peptides from Tabl...
HSV-1 peptides from Table 4 (n = 40, detailed in Methods) were tested with PBMCs from 20 individuals with HSV-1 infection. Each column represents one participant; 1–7 are detailed in Table 1. Each row lists a peptide with 1 or more positive ELISPOT results. Green cells represent possible reactivities based on the participant bearing an HLA allele corresponding to the peptide tested, but for which the ORFeome screen with the listed HLA allele and ORF, and peptide ELISPOT, were negative. Blue cells are similar, but the ORFeome screen was positive and the peptide ELISPOT with the indicated peptide was negative. Red cells represent ORFs for which both the ORFeome screen with the listed HLA allele and ORF, and the ELISPOT for at least one peptide in the ORF, were positive. Numbers in red cells are positive ELISPOT results in units of net IFN-γ SFU/106 PBMCs.