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

Shailbala Singh,Scott Anthony,Guojun Yang,K Sastry,Michael Barry,Kimberly Schluns

doi:10.3390/vaccines4010007

Shailbala Singh, Scott Anthony + Show 4 more

Open Access

https://doi.org/10.3390/vaccines4010007

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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.

Highlights

Since the majority of pathogenic infections are initiated at the mucosal surfaces, induction of robust immunity at these sites is critical for protection [1,2,3,4,5,6]
Studies suggest that mucosal specific integrins, such as α4β7, and chemokine receptors, such as CCR9, CR10, and CXCR3, expressed in the mucosal microenvironment could be involved in achieving broadly-disseminated mucosal immunity but the chemokine signaling mechanisms that direct the vaccine-induced T cell responses to female reproductive tract (FRT)
We used the adoptive transfer of ovalbumin (OVA)-specific OT-I TCR transgenic (Tg) CD8+ T cells as a model system to explore the kinetics of antigen-specific T cells in the FRT of the mice following

Summary

Introduction

Since the majority of pathogenic infections are initiated at the mucosal surfaces, induction of robust immunity at these sites is critical for protection [1,2,3,4,5,6]. For sexually-transmitted pathogens, such as the human immunodeficiency virus (HIV) and human papilloma virus (HPV), generation of antigen-specific cell-mediated immunity in the female reproductive tract (FRT) is essential so that. The effective route for vaccine-mediated induction of CD8 T cell responses in the FRT is less well established [8,10,11,12]. Studies suggest that mucosal specific integrins, such as α4β7, and chemokine receptors, such as CCR9, CR10, and CXCR3, expressed in the mucosal microenvironment could be involved in achieving broadly-disseminated mucosal immunity but the chemokine signaling mechanisms that direct the vaccine-induced T cell responses to FRT remain poorly defined [13,14,15,16]. To develop effective vaccines against sexually-transmitted infections, an understanding of the phenotype and kinetics of development and persistence of the CD8+ T cell immune response in FRT is essential

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Conclusion