PMID- 29899087
OWN - NLM
STAT- MEDLINE
DCOM- 20180817
LR  - 20190918
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 92
IP  - 16
DP  - 2018 Aug 15
TI  - Human Asymptomatic Epitope Peptide/CXCL10-Based Prime/Pull Vaccine Induces Herpes 
      Simplex Virus-Specific Gamma Interferon-Positive CD107(+) CD8(+) T Cells That 
      Infiltrate the Corneas and Trigeminal Ganglia of Humanized HLA Transgenic Rabbits 
      and Protect against Ocular Herpes Challenge.
LID - 10.1128/JVI.00535-18 [doi]
LID - e00535-18
AB  - Herpes simplex virus 1 (HSV-1) is a prevalent human pathogen that infects the 
      cornea, causing potentially blinding herpetic disease. A clinical herpes vaccine 
      is still lacking. In the present study, a novel prime/pull vaccine was tested in 
      a human leukocyte antigen (HLA) transgenic rabbit model of ocular herpes (HLA Tg 
      rabbits). Three peptide epitopes were selected, from the HSV-1 membrane 
      glycoprotein C (UL44(400-408)), the DNA replication binding helicase 
      (UL9(196-204)), and the tegument protein (UL25(572-580)), all preferentially 
      recognized by CD8(+) T cells from "naturally protected" HSV-1-seropositive 
      healthy asymptomatic (ASYMP) individuals (who never had recurrent corneal 
      herpetic disease). HLA Tg rabbits were immunized with a mixture of these three 
      ASYMP CD8(+) T cell peptide epitopes (UL44(400-408), UL9(196-204), and 
      UL25(572-580)), which were delivered subcutaneously with CpG(2007) adjuvant 
      (prime). Fifteen days later, half of the rabbits received a topical ocular 
      treatment with a recombinant neurotropic adeno-associated virus type 8 (AAV8) 
      vector expressing the T cell-attracting CXCL10 chemokine (pull). The frequency 
      and function of HSV-specific CD8(+) T cells induced by the prime/pull vaccine 
      were assessed in the peripheral blood, cornea, and trigeminal ganglion (TG). 
      Compared to the cells generated in response to peptide immunization alone, the 
      peptide/CXCL10 prime/pull vaccine generated frequent polyfunctional gamma 
      interferon-positive (IFN-gamma(+)) CD107(+) CD8(+) T cells that infiltrated both the 
      cornea and TG. CD8(+) T cell mobilization into the cornea and TG of 
      prime/pull-vaccinated rabbits was associated with a significant reduction in 
      corneal herpesvirus infection and disease following an ocular HSV-1 (strain 
      McKrae) challenge. These findings draw attention to the novel prime/pull vaccine 
      strategy for mobilizing antiviral CD8(+) T cells into tissues to protect against 
      herpesvirus infection and disease.IMPORTANCE There is an urgent need for a 
      vaccine against widespread herpes simplex virus infections. The present study 
      demonstrates that immunization of HLA transgenic rabbits with a peptide/CXCL10 
      prime/pull vaccine triggered mobilization of HSV-specific CD8(+) T cells locally 
      into the cornea and TG, the sites of acute and latent herpesvirus infections, 
      respectively. Mobilization of antiviral CD8(+) T cells into the cornea and TG of 
      rabbits that received the prime/pull vaccine was associated with protection 
      against ocular herpesvirus infection and disease following an ocular HSV-1 
      challenge. These results highlight the importance of the prime/pull vaccine 
      strategy to bolster the number and function of protective CD8(+) T cells within 
      infected tissues.
CI  - Copyright (c) 2018 American Society for Microbiology.
FAU - Khan, Arif A
AU  - Khan AA
AD  - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, 
      School of Medicine, University of California, Irvine, Irvine, California, USA.
FAU - Srivastava, Ruchi
AU  - Srivastava R
AD  - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, 
      School of Medicine, University of California, Irvine, Irvine, California, USA.
FAU - Vahed, Hawa
AU  - Vahed H
AD  - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, 
      School of Medicine, University of California, Irvine, Irvine, California, USA.
FAU - Roy, Soumyabrata
AU  - Roy S
AD  - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, 
      School of Medicine, University of California, Irvine, Irvine, California, USA.
FAU - Walia, Sager S
AU  - Walia SS
AD  - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, 
      School of Medicine, University of California, Irvine, Irvine, California, USA.
FAU - Kim, Grace J
AU  - Kim GJ
AD  - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, 
      School of Medicine, University of California, Irvine, Irvine, California, USA.
FAU - Fouladi, Mona A
AU  - Fouladi MA
AD  - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, 
      School of Medicine, University of California, Irvine, Irvine, California, USA.
FAU - Yamada, Taikun
AU  - Yamada T
AD  - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, 
      School of Medicine, University of California, Irvine, Irvine, California, USA.
FAU - Ly, Vincent T
AU  - Ly VT
AD  - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, 
      School of Medicine, University of California, Irvine, Irvine, California, USA.
FAU - Lam, Cynthia
AU  - Lam C
AD  - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, 
      School of Medicine, University of California, Irvine, Irvine, California, USA.
FAU - Lou, Anthony
AU  - Lou A
AD  - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, 
      School of Medicine, University of California, Irvine, Irvine, California, USA.
FAU - Nguyen, Vivianna
AU  - Nguyen V
AD  - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, 
      School of Medicine, University of California, Irvine, Irvine, California, USA.
FAU - Boldbaatar, Undariya
AU  - Boldbaatar U
AD  - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, 
      School of Medicine, University of California, Irvine, Irvine, California, USA.
FAU - Geertsema, Roger
AU  - Geertsema R
AD  - University Laboratory Animal Resources, University of California, Irvine, Irvine, 
      California, USA.
FAU - Fraser, Nigel W
AU  - Fraser NW
AD  - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, 
      School of Medicine, University of California, Irvine, Irvine, California, USA.
FAU - BenMohamed, Lbachir
AU  - BenMohamed L
AD  - Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, 
      School of Medicine, University of California, Irvine, Irvine, California, USA 
      Lbenmoha@uci.edu.
AD  - Department of Molecular Biology & Biochemistry, School of Medicine, University of 
      California, Irvine, Irvine, California, USA.
AD  - Institute for Immunology, School of Medicine, University of California, Irvine, 
      Irvine, California, USA.
LA  - eng
GR  - UL1 TR001414/TR/NCATS NIH HHS/United States
GR  - R01 EY026103/EY/NEI NIH HHS/United States
GR  - R41 AI138764/AI/NIAID NIH HHS/United States
GR  - R01 EY024618/EY/NEI NIH HHS/United States
GR  - R21 AI110902/AI/NIAID NIH HHS/United States
GR  - R01 EY019896/EY/NEI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20180731
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (CXCL10 protein, human)
RN  - 0 (Chemokine CXCL10)
RN  - 0 (Epitopes)
RN  - 0 (HLA Antigens)
RN  - 0 (Herpes Simplex Virus Vaccines)
RN  - 0 (Lysosomal-Associated Membrane Protein 1)
RN  - 0 (Vaccines, Subunit)
RN  - 82115-62-6 (Interferon-gamma)
SB  - IM
MH  - Animals
MH  - Animals, Genetically Modified
MH  - CD8-Positive T-Lymphocytes/*immunology
MH  - Chemokine CXCL10/administration & dosage/*metabolism
MH  - Cornea/*immunology
MH  - Disease Models, Animal
MH  - Epitopes/immunology
MH  - HLA Antigens/genetics/metabolism
MH  - Herpes Simplex Virus Vaccines/administration & dosage/*immunology
MH  - Humans
MH  - Interferon-gamma/analysis
MH  - Keratitis, Herpetic/pathology/*prevention & control/virology
MH  - Lysosomal-Associated Membrane Protein 1/analysis
MH  - Rabbits
MH  - Simplexvirus/immunology/isolation & purification
MH  - T-Lymphocyte Subsets/*immunology
MH  - Trigeminal Ganglion/*immunology
MH  - Vaccines, Subunit/administration & dosage/immunology
MH  - Viral Load
PMC - PMC6069188
OTO - NOTNLM
OT  - CD8+ T cell
OT  - CXCL10
OT  - HLA transgenic rabbit
OT  - HSV-1
OT  - herpes
OT  - herpes simplex
OT  - ocular
OT  - prime/pull
OT  - prime/pull vaccine
EDAT- 2018/06/15 06:00
MHDA- 2018/08/18 06:00
PMCR- 2019/01/31
CRDT- 2018/06/15 06:00
PHST- 2018/03/28 00:00 [received]
PHST- 2018/05/21 00:00 [accepted]
PHST- 2018/06/15 06:00 [pubmed]
PHST- 2018/08/18 06:00 [medline]
PHST- 2018/06/15 06:00 [entrez]
PHST- 2019/01/31 00:00 [pmc-release]
AID - JVI.00535-18 [pii]
AID - 00535-18 [pii]
AID - 10.1128/JVI.00535-18 [doi]
PST - epublish
SO  - J Virol. 2018 Jul 31;92(16):e00535-18. doi: 10.1128/JVI.00535-18. Print 2018 Aug 
      15.