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Cited by 110Herpesvirus Infections and TreatmentsImmunotherapy and Immune Responsesvaccines and immunoinformatics approaches

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A genital tract peptide epitope vaccine targeting TLR-2 efficiently induces local and systemic CD8+ T cells and protects against herpes simplex virus type 2 challenge

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Zhang, X, Chentoufi, A A, Dasgupta, G, Nesburn, A B, Wu, M, Zhu, X, Carpenter, D, Wechsler, S L, You, S, BenMohamed, L·2009·Mucosal Immunology
DOI 10.1038/mi.2008.81PMC PMC4509510
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Abstract

The next generation of needle-free mucosal vaccines is being rationally designed according to rules that govern the way in which the epitopes are recognized by and stimulate the genital mucosal immune system. We hypothesized that synthetic peptide epitopes extended with an agonist of Toll-like receptor 2 (TLR-2), that are abundantly expressed by dendritic and epithelial cells of the vaginal mucosa, would lead to induction of protective immunity against genital herpes. To test this hypothesis, we intravaginally (IVAG) immunized wild-type B6, TLR-2 (TLR2(-/-)) or myeloid differentiation factor 88 deficient (MyD88(-/-)) mice with a herpes simplex virus type 2 (HSV-2) CD8+ T-cell peptide epitope extended by a palmitic acid moiety (a TLR-2 agonist). IVAG delivery of the lipopeptide generated HSV-2-specific memory CD8+ cytotoxic T cells both locally in the genital tract draining lymph nodes and systemically in the spleen. Moreover, lipopeptide-immunized TLR2(-/-) and MyD88(-/-) mice developed significantly less HSV-specific CD8+ T-cell response, earlier death, faster disease progression, and higher vaginal HSV-2 titers compared to lipopeptide-immunized wild-type B6 mice. IVAG immunization with self-adjuvanting lipid-tailed peptides appears to be a novel mucosal vaccine approach, which has attractive practical and immunological features.

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Metadata

Authors
Zhang, X., Chentoufi, A. A., Dasgupta, G., Nesburn, A. B., Wu, M., Zhu, X., Carpenter, D., Wechsler, S. L., You, S., & BenMohamed, L.
Affiliations
  • University of California, Irvine (US)
  • Inserm (FR)
Corresponding author
BenMohamed, L
ORCID
Venue
Mucosal Immunology
Publisher
Elsevier BV
Published
2009-03
Volume
2
Issue
2
Pages
129-143
ISSN
1933-0219 (ISSN-L)
DOI
10.1038/mi.2008.81
PMC
PMC4509510
OpenAlex
W2119216636
Cited by
110
References
1
Citations by year
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FWCI
8.25
Type
journal article
Language
en
Open access
Licence
Locations
  • Mucosal Immunology (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Research to Prevent Blindness
  • Discovery Eye Foundation
  • Ögonfonden
  • National Institutes of Health
  • National Eye Institute (EY 16663, EY 14900, EY15225, R01EY014900, R01EY024618, R01EY015225, R24EY016663, R01EY019896)
Topics
  • Health Sciences › Medicine › Infectious Diseases › Herpesvirus Infections and Treatments
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
Keywords
herpes simplex virus type 2, genital herpes, lipopeptides, mucosal vaccines, intravaginal immunization, CD8+ T cells, cytotoxic T lymphocytes, MyD88, TLR2-deficient mice, vaginal mucosa, genital tract immunity, protective immunity
MeSH terms
Adjuvants, Immunologic, Administration, Intravaginal, Animals, Female, Herpes Genitalis, Mucous Membrane, Herpesvirus 2, Human, CD8-Positive T-Lymphocytes, Epitopes, T-Lymphocyte, Herpes Simplex Virus Vaccines, Toll-Like Receptor 2, Mice, Myeloid Differentiation Factor 88, Lipopeptides

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