title: Intranasal Vaccination Affords Localization and Persistence of Antigen-Specific CD8⁺ T Lymphocytes in the Female Reproductive Tract.
abstract: 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.
authors.affiliation: Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77054, USA. ssingh1@mdanderson.org.
authors.forename: Shailbala
authors.initials: S
authors.lastname: Singh
authors.affiliation: Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77054, USA. kschluns@mdanderson.org.|Immunology Graduate Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA. kschluns@mdanderson.org.
authors.forename: Kimberly S
authors.initials: KS
authors.lastname: Schluns
authors.affiliation: Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77054, USA. gyang3@mdanderson.org.
authors.forename: Guojun
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77054, USA. scottmanthony@gmail.com.|Immunology Graduate Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA. scottmanthony@gmail.com.
authors.forename: Scott M
authors.initials: SM
authors.lastname: Anthony
authors.affiliation: Department of Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA. Barry.Michael@mayo.edu.|Department of Molecular Medicine, Mayo Clinic, Rochester, MN 55905, USA. Barry.Michael@mayo.edu.|Division of Infectious Diseases, Mayo Clinic, Rochester, MN 55905, USA. Barry.Michael@mayo.edu.|Translational Immunovirology Program, Mayo Clinic, Rochester, MN 55905, USA. Barry.Michael@mayo.edu.|Department of Immunology, Mayo Clinic, Rochester, MN 55905, USA. Barry.Michael@mayo.edu.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Barry
authors.affiliation: Department of Immunology, The University of Texas M.D. Anderson Cancer Center, Houston, TX 77054, USA. jsastry@mdanderson.org.|Immunology Graduate Program, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, TX 77030, USA. jsastry@mdanderson.org.
authors.forename: K Jagannadha
authors.initials: KJ
authors.lastname: Sastry
keywords: CD8+ T cells; Female reproductive tract; intranasal immunization