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J Virol. 2018 Mar 28;92(8). pii: e02156-17. doi: 10.1128/JVI.02156-17. Print 2018 Apr 15.

Laser Adjuvant-Assisted Peptide Vaccine Promotes Skin Mobilization of Dendritic Cells and Enhances Protective CD8+ TEM and TRM Cell Responses against Herpesvirus Infection and Disease.

Author information

1
Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, California, USA.
2
INSERM, U1043, CNRS, U5282, Toulouse, France.
3
Université Paul Sabatier, Toulouse, France.
4
Laboratory of Cellular and Molecular Immunology, Gavin Herbert Eye Institute, University of California, Irvine, School of Medicine, Irvine, California, USA Lbenmoha@uci.edu.
5
Department of Molecular Biology & Biochemistry, University of California, Irvine, School of Medicine, Irvine, California, USA.
6
Institute for Immunology, University of California, Irvine, School of Medicine, Irvine, California, USA.
#
Contributed equally

Abstract

There is an urgent need for chemical-free and biological-free safe adjuvants to enhance the immunogenicity of vaccines against widespread viral pathogens, such as herpes simplex virus 2 (HSV-2), that infect a large proportion of the world human population. In the present study, we investigated the safety, immunogenicity, and protective efficacy of a laser adjuvant-assisted peptide (LAP) vaccine in the B6 mouse model of genital herpes. This LAP vaccine and its laser-free peptide (LFP) vaccine analog contain the immunodominant HSV-2 glycoprotein B CD8+ T cell epitope (HSV-gB498-505) covalently linked with the promiscuous glycoprotein D CD4+ T helper cell epitope (HSV-gD49-89). Prior to intradermal delivery of the LAP vaccine, the lower-flank shaved skin of B6 or CD11c/eYFP transgenic mice received a topical skin treatment with 5% imiquimod cream and then was exposed for 60 s to a laser, using the FDA-approved nonablative diode. Compared to the LFP vaccine, the LAP vaccine (i) triggered mobilization of dendritic cells (DCs) in the skin, which formed small spots along the laser-treated areas, (ii) induced phenotypic and functional maturation of DCs, (iii) stimulated long-lasting HSV-specific effector memory CD8+ T cells (TEM cells) and tissue-resident CD8+ T cells (TRM cells) locally in the vaginal mucocutaneous tissues (VM), and (iv) induced protective immunity against genital herpes infection and disease. As an alternative to currently used conventional adjuvants, the chemical- and biological-free laser adjuvant offers a well-tolerated, simple-to-produce method to enhance mass vaccination for widespread viral infections.IMPORTANCE Herpes simplex viruses 1 and 2 (HSV-1 and HSV-2) infect a large proportion of the world population. There is an urgent need for chemical-free and biological-free safe adjuvants that would advance mass vaccination against the widespread herpes infections. The present study demonstrates that immunization with a laser-assisted herpes peptide vaccine triggered skin mobilization of dendritic cells (DCs) that stimulated strong and long-lasting HSV-specific effector memory CD8+ T cells (TEM cells) and tissue-resident CD8+ T cells (TRM cells) locally in the vaginal mucocutaneous tissues. The induced local CD8+ T cell response was associated with protection against genital herpes infection and disease. These results draw attention to chemical- and biological-free laser adjuvants as alternatives to currently used conventional adjuvants to enhance mass vaccination for widespread viral infections, such as those caused by HSV-1 and HSV-2.

KEYWORDS:

CD4+ T cells; CD8+ T cells; dendritic cells; genital herpes; herpes simplex virus; laser adjuvant

PMID:
29437976
PMCID:
PMC5874417
DOI:
10.1128/JVI.02156-17
[Indexed for MEDLINE]
Free PMC Article

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