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Cutting Edge: The Use of Topical Aminoglycosides as an Effective Pull in “Prime and Pull” Vaccine Strategy

Smita Gopinath, Peiwen Lu and Akiko Iwasaki
J Immunol April 1, 2020, 204 (7) 1703-1707; DOI: https://doi.org/10.4049/jimmunol.1900462
Smita Gopinath
*Howard Hughes Medical Institute, Chevy Chase, MD 20815;
†Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519; and
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Peiwen Lu
†Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519; and
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Akiko Iwasaki
*Howard Hughes Medical Institute, Chevy Chase, MD 20815;
†Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06519; and
‡Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06519
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Key Points

  • Intravaginal neomycin can pull CD8 T cells to the vaginal mucosa.

  • Neomycin-recruited CD8 T cells become tissue resident and protect mice from HSV-2.

  • Neomycin can replace recombinant chemokine CXCL10 in prime and pull vaccine.

Abstract

The presence of tissue-resident memory T cells at barrier tissues is critical for long-lasting protective immune responses. Previous work has shown that tissue-resident memory T cells can be established by “pulling” virus-specific effector T cells from circulation to the genital mucosa via topical vaginal application of chemokines in mice. Once established, these cells protect hosts against genital herpes infection. We recently showed that vaginal application of aminoglycoside antibiotics induces robust activation of the IFN signaling pathway, including upregulation of chemokine expression within the tissue in mice. In this study, we show that a single topical application of neomycin, an inexpensive and vaginally nontoxic antibiotic, is sufficient to pull CD8 T cells to the vaginal mucosa and provide protection against genital herpes infection in mice.

Footnotes

  • This work was in part supported by the Howard Hughes Medical Institute (to A.I.) and by funding from the National Institutes of Health to (A.I.) (R01AI054359, R01EB000487, and R01AI127429). S.G. and P.L. are recipients of James Hudson Brown–Alexander Brown Coxe postdoctoral fellowships at Yale University.

  • The online version of this article contains supplemental material.

  • Abbreviations used in this article:

    TRM
    tissue-resident memory T cell
    WT
    wild-type.

  • Received April 24, 2019.
  • Accepted February 1, 2020.
  • Copyright © 2020 by The American Association of Immunologists, Inc.
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The Journal of Immunology: 204 (7)
The Journal of Immunology
Vol. 204, Issue 7
1 Apr 2020
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Cutting Edge: The Use of Topical Aminoglycosides as an Effective Pull in “Prime and Pull” Vaccine Strategy
Smita Gopinath, Peiwen Lu, Akiko Iwasaki
The Journal of Immunology April 1, 2020, 204 (7) 1703-1707; DOI: 10.4049/jimmunol.1900462

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Cutting Edge: The Use of Topical Aminoglycosides as an Effective Pull in “Prime and Pull” Vaccine Strategy
Smita Gopinath, Peiwen Lu, Akiko Iwasaki
The Journal of Immunology April 1, 2020, 204 (7) 1703-1707; DOI: 10.4049/jimmunol.1900462
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