June 2017
Volume 58, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2017
Human Asymptomatic Epitopes Identified from the Herpes Simplex Virus Tegument Protein VP13/14 (UL47) Preferentially Recall Polyfunctional Effector Memory CD44highCD62LlowCD8+ TEM Cells and Protect “Humanized” HLA-A*02:01 Transgenic Mice Against Ocular Herpes
Author Affiliations & Notes
  • Anthony Nesburn
    Gavin Herbert Eye Institute, University of California Irvine, IRVINE, California, United States
  • Ruchi Srivastava
    Gavin Herbert Eye Institute, University of California Irvine, IRVINE, California, United States
  • Lbachir BenMohamed
    Gavin Herbert Eye Institute, University of California Irvine, IRVINE, California, United States
  • Footnotes
    Commercial Relationships   Anthony Nesburn, None; Ruchi Srivastava, None; Lbachir BenMohamed, None
  • Footnotes
    Support  This work is supported by Public Health Service research grants EY14900, EY019896 and EY024618 from National Eye Institute (NEI), from National Institutes of Health (NIH), from The Discovery Center for Eye Research (DCER) and from a Research to Prevent Blindness (RPB) grant.
Investigative Ophthalmology & Visual Science June 2017, Vol.58, 3630. doi:
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    • Get Citation

      Anthony Nesburn, Ruchi Srivastava, Lbachir BenMohamed; Human Asymptomatic Epitopes Identified from the Herpes Simplex Virus Tegument Protein VP13/14 (UL47) Preferentially Recall Polyfunctional Effector Memory CD44highCD62LlowCD8+ TEM Cells and Protect “Humanized” HLA-A*02:01 Transgenic Mice Against Ocular Herpes
      . Invest. Ophthalmol. Vis. Sci. 2017;58(8):3630.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Herpes simplex virus type 1 (HSV-1) infection is widespread among humans. The HSV-1 virion protein 13/14 (VP13/14), also known as UL47, is a tegument antigen (Ag) targeted by CD8+ T cells from HSV-seropositive individuals. However, whether VP13/14-specific CD8+ T cells play a role in the “natural” protection seen in asymptomatic (ASYMP) individuals (who never had a clinical herpetic disease) has not been elucidated.

Methods : Using predictive computer-assisted algorithms, we identify 10 potential HLA-A*02:01-restricted CD8+ T cell epitopes from the 693 amino acids sequence of VP13/14 protein.

Results : Three out of ten epitopes exhibited high to moderate binding affinity to soluble HLA-A*02:01 molecules. The phenotype and function of effector CD8+ T cells specific for each epitope were compared in HLA-A*0201 positive ASYMP vs. SYMP individuals (who have frequent clinical herpetic diseases), using a combination of tetramer frequency, granzyme B, granzyme K, perforin, CD107a/b cytotoxic degranulation, and IFN-g production. Higher frequency of multi-functional effector CD8+ T cells directed against three epitopes, VP13/14286-294, VP13/14504-512 and VP13/14544-552, was predominantly detected in ten ASYMP compared to ten SYMP individuals. The three epitopes also predominantly recalled more CD45RAlowCD44highCCR7lowCD62LlowCD8+ effector memory T cells (TEM) in ASYMP individuals. Moreover, immunization of HLA-A*02:01 transgenic mice with the three “ASYMP” CD8+ TEM cell epitopes induced robust and polyfunctional HSV-specific CD8+ TEM cells associated with a strong protective immunity against ocular herpes infection and disease.

Conclusions : Our findings outlining phenotypic and functional features of protective HSV-1 VP13/14-specific CD8+ T cells should guide development of a safe and effective T-cell-based herpes vaccine.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

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