Evidence map›Paper›PMID 25617474›Full record

ArticleJournal of immunology (Baltimore, Md. : 1950)2015

HLA-A02:01-restricted epitopes identified from the herpes simplex virus tegument protein VP11/12 preferentially recall polyfunctional effector memory CD8+ T cells from seropositive asymptomatic individuals and protect humanized HLA-A*02:01 transgenic mice against ocular herpes.

Ruchi Srivastava, Arif A Khan, Doran Spencer, Hawa Vahed, Patricia P Lopes, Nhi Thi Uyen Thai, Christine Wang, Thanh T Pham, Jiawei Huang, Vanessa M Scarfone and 3 more

Abstract read
In one paragraph

Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.

0numbers the graph read from it
0cells of the map it votes in
35citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

35 citing papers in PubMed.

  1. Review
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  9. Article
  10. Upregulation of Multiple CD8Journal of immunology (Baltimore, Md. : 1950) · 2020
    Article
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  12. Review
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  14. Review
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  18. Observational
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Ruchi SrivastavaLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697;
Arif A KhanLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697;
Doran SpencerLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697;
Hawa VahedLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697;
Patricia P LopesLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697;
Nhi Thi Uyen ThaiLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697;
Christine WangLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697;
Thanh T PhamLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697;
Jiawei HuangLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697;
Vanessa M ScarfoneStem Cell Research Center, University of California Irvine, Irvine, CA 92697;
Anthony B NesburnLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697;
Steven L WechslerLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697; Virology Research, Gavin Herbert Eye Institute and Department of Ophthalmology, University of California Irvine, School of Medicine, Irvine, CA 92697; Department of Microbiology and Molecular Genetics, University of California Irvine, School of Medicine, Irvine, CA 92697; Center for Virus Research, University of California Irvine, Irvine, CA 92697;
Lbachir BenMohamedLaboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California Irvine, School of Medicine, Irvine, CA 92697; Department of Molecular Biology and Biochemistry, University of California Irvine, School of Medicine, Irvine, CA 92697; and Institute for Immunology, University of California Irvine, School of Medicine, Irvine, CA 92697 Lbenmoha@uci.edu.

Funding

Corneal HSV-1: LAT's Anti-Apoptosis Activity and LatencyR01EY013191 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI WECHSLER, STEVEN L · 2001 to 2013
$6.9M
Therapeutic Ocular HSV Vaccine in HLA Transgenic RabbitsR01EY019896 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI BENMOHAMED, LBACHIR · 2010 to 2025
$5.1M
Ocular Mucsoal Immunity Induced by HSV-1 LipopeptidesR01EY014900 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI BENMOHAMED, LBACHIR · 2003 to 2014
$3.1M
Blockade of T-cell Co-Inhibitory Pathways & Immunotherapy to Prevent Ocular HerpeR01EY024618 · NEI · UNIVERSITY OF CALIFORNIA-IRVINE · PI BENMOHAMED, LBACHIR · 2014 to 2016
$1.2M
HSV-1 LAT miRNAs: Neurovirulence, reactivation, mechanismR56AI098985 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI WECHSLER, STEVEN L · 2013 to 2013
$421k
Corneal HSV-1: Newly discovered LAT miRNAs and latencyR56AI093133 · NIAID · UNIVERSITY OF CALIFORNIA-IRVINE · PI WECHSLER, STEVEN L · 2011 to 2011
$383k
NEI NIH HHS EY013191NEI NIH HHS EY019896NEI NIH HHS EY024618NEI NIH HHS EY14900NEI NIH HHS R01 EY013191NEI NIH HHS R01 EY014900NEI NIH HHS R01 EY019896NEI NIH HHS R01 EY024618NIAID NIH HHS 1R56AI093133NIAID NIH HHS 1R56AI098985NIAID NIH HHS R56 AI093133NIAID NIH HHS R56 AI098985
6 · The paper itself

Abstract

The HSV type 1 tegument virion phosphoprotein (VP) 11/12 (VP11/12) is a major Ag targeted by CD8(+) T cells from HSV-seropositive individuals. However, whether and which VP11/12 epitope-specific CD8(+) T cells play a role in the "natural" protection seen in seropositive healthy asymptomatic (ASYMP) individuals (who have never had clinical herpes disease) remain to be determined. In this study, we used multiple prediction computer-assisted algorithms to identify 10 potential HLA-A*02:01-restricted CD8(+) T cell epitopes from the 718-aa sequence of VP11/12. Three of 10 epitopes exhibited high-to-moderate binding affinity to HLA-A*02:01 molecules. In 10 sequentially studied HLA-A*02:01-positive and HSV-1-seropositive ASYMP individuals, the most frequent, robust, and polyfunctional effector CD8(+) T cell responses, as assessed by a combination of tetramer frequency, granzyme B, granzyme K, perforin, CD107(a/b) cytotoxic degranulation, IFN-γ, and multiplex cytokines assays, were predominantly directed against three epitopes: VP11/1266-74, VP11/12220-228, and VP11/12702-710. Interestingly, ASYMP individuals had a significantly higher proportion of CD45RA(low)CCR7(low)CD44(high)CD62L(low)CD27(low)CD28(low)CD8(+) effector memory CD8(+) T cells (TEMs) specific to the three epitopes, compared with symptomatic individuals (with a history of numerous episodes of recurrent ocular herpetic disease). Moreover, immunization of HLA-A*02:01 transgenic mice with the three ASYMP CD8(+) TEM cell epitopes induced robust and polyfunctional epitope-specific CD8(+) TEM cells that were associated with a strong protective immunity against ocular herpes infection and disease. Our findings outline phenotypic and functional features of protective HSV-specific CD8(+) T cells that should guide the development of an effective T cell-based herpes vaccine.

Indexed as

AdolescentAdultAgedAlgorithmsAmino Acid SequenceAnimalsAntigens, ViralAsymptomatic DiseasesCD8-Positive T-LymphocytesEpitopes, T-LymphocyteFemaleHerpesvirus 1, HumanHerpesvirus 2, HumanHLA-A2 AntigenHumansImmunity, CellularAntigens, ViralEpitopes, T-LymphocyteHLA-A*02:01 antigenHLA-A2 AntigenPeptidesUL46 protein, Human herpesvirus 1Viral Proteins

Identifiers

PMID25617474
PMCPMC4340763

What OpenQuestion holds

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Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.