Intranasal Vaccination Affords Localization and Persistence of Antigen-Specific CD8+ T Lymphocytes in the Female Reproductive Tract

Immunization strategies generating large numbers of antigen-specific T cells in the female reproductive tract (FRT) can provide barrier protection against sexually-transmitted pathogens, such as the human immunodeficiency virus (HIV) and human papillomaviruses (HPV). The kinetics and mechanisms of r...

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Main Authors: Shailbala Singh, Kimberly S. Schluns, Guojun Yang, Scott M. Anthony, Michael A. Barry, K. Jagannadha Sastry
Format: Article
Language:English
Published: MDPI AG 2016-03-01
Series:Vaccines
Subjects:
Online Access:http://www.mdpi.com/2076-393X/4/1/7
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author Shailbala Singh
Kimberly S. Schluns
Guojun Yang
Scott M. Anthony
Michael A. Barry
K. Jagannadha Sastry
author_facet Shailbala Singh
Kimberly S. Schluns
Guojun Yang
Scott M. Anthony
Michael A. Barry
K. Jagannadha Sastry
author_sort Shailbala Singh
collection DOAJ
description Immunization strategies generating large numbers of antigen-specific T cells in the female reproductive tract (FRT) can provide barrier protection against sexually-transmitted pathogens, such as the human immunodeficiency virus (HIV) and human papillomaviruses (HPV). The kinetics and mechanisms of regulation of vaccine-induced adaptive T cell-mediated immune responses in FRT are less well defined. We present here evidence for intranasal delivery of the model antigen ovalbumin (OVA) along with alpha-galactosylceramide adjuvant as a protein vaccine to induce significantly higher levels of antigen-specific effector and memory CD8+ T cells in the FRT, relative to other systemic and mucosal tissues. Antibody blocking of the CXCR3 receptor significantly reduced antigen-specific CD8+ T cells subsequent to intranasal delivery of the protein vaccine suggesting an important role for the CXCR3 chemokine-receptor signaling for T cell trafficking. Further, intranasal vaccination with an adenoviral vector expressing OVA or HIV-1 envelope was as effective as intramuscular vaccination for generating OVA- or ENV-specific immunity in the FRT. These results support the application of the needle-free intranasal route as a practical approach to delivering protein as well as DNA/virus vector-based vaccines for efficient induction of effector and memory T cell immunity in the FRT.
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spelling doaj.art-f9351224eb244887a25fd556074173f12022-12-22T04:20:05ZengMDPI AGVaccines2076-393X2016-03-0141710.3390/vaccines4010007vaccines4010007Intranasal Vaccination Affords Localization and Persistence of Antigen-Specific CD8+ T Lymphocytes in the Female Reproductive TractShailbala Singh0Kimberly S. Schluns1Guojun Yang2Scott M. Anthony3Michael A. Barry4K. Jagannadha Sastry5Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77054, USADepartment of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77054, USADepartment of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77054, USADepartment of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77054, USADepartment of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USADepartment of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77054, USAImmunization strategies generating large numbers of antigen-specific T cells in the female reproductive tract (FRT) can provide barrier protection against sexually-transmitted pathogens, such as the human immunodeficiency virus (HIV) and human papillomaviruses (HPV). The kinetics and mechanisms of regulation of vaccine-induced adaptive T cell-mediated immune responses in FRT are less well defined. We present here evidence for intranasal delivery of the model antigen ovalbumin (OVA) along with alpha-galactosylceramide adjuvant as a protein vaccine to induce significantly higher levels of antigen-specific effector and memory CD8+ T cells in the FRT, relative to other systemic and mucosal tissues. Antibody blocking of the CXCR3 receptor significantly reduced antigen-specific CD8+ T cells subsequent to intranasal delivery of the protein vaccine suggesting an important role for the CXCR3 chemokine-receptor signaling for T cell trafficking. Further, intranasal vaccination with an adenoviral vector expressing OVA or HIV-1 envelope was as effective as intramuscular vaccination for generating OVA- or ENV-specific immunity in the FRT. These results support the application of the needle-free intranasal route as a practical approach to delivering protein as well as DNA/virus vector-based vaccines for efficient induction of effector and memory T cell immunity in the FRT.http://www.mdpi.com/2076-393X/4/1/7Female reproductive tractCD8+ T cellsintranasal immunization
spellingShingle Shailbala Singh
Kimberly S. Schluns
Guojun Yang
Scott M. Anthony
Michael A. Barry
K. Jagannadha Sastry
Intranasal Vaccination Affords Localization and Persistence of Antigen-Specific CD8+ T Lymphocytes in the Female Reproductive Tract
Vaccines
Female reproductive tract
CD8+ T cells
intranasal immunization
title Intranasal Vaccination Affords Localization and Persistence of Antigen-Specific CD8+ T Lymphocytes in the Female Reproductive Tract
title_full Intranasal Vaccination Affords Localization and Persistence of Antigen-Specific CD8+ T Lymphocytes in the Female Reproductive Tract
title_fullStr Intranasal Vaccination Affords Localization and Persistence of Antigen-Specific CD8+ T Lymphocytes in the Female Reproductive Tract
title_full_unstemmed Intranasal Vaccination Affords Localization and Persistence of Antigen-Specific CD8+ T Lymphocytes in the Female Reproductive Tract
title_short Intranasal Vaccination Affords Localization and Persistence of Antigen-Specific CD8+ T Lymphocytes in the Female Reproductive Tract
title_sort intranasal vaccination affords localization and persistence of antigen specific cd8 t lymphocytes in the female reproductive tract
topic Female reproductive tract
CD8+ T cells
intranasal immunization
url http://www.mdpi.com/2076-393X/4/1/7
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