Interferon-λ Improves the Efficacy of Intranasally or Rectally Administered Influenza Subunit Vaccines by a Thymic Stromal Lymphopoietin-Dependent Mechanism.

Liang Ye,Hans Henrik Gad,Li Ching Ong,Annette Ohnemus,Peter Staeheli,Daniel Schnepf,Rune Hartmann,Nils Lycke

doi:10.3389/fimmu.2021.749325

Abstract

Previous work showed that interferon-λ (IFN-λ) can trigger the synthesis of thymic stromal lymphopoietin (TSLP) by specialized epithelial cells in the upper airways of mice, thereby improving the performance of intranasally administered influenza vaccines. Here we demonstrate that protein-only influenza vaccines containing either IFN-λ or TSLP boosted antigen-specific IgG1 and IgA responses and enhanced the resistance of mice to influenza virus challenge, irrespective of whether the vaccines were applied via the intranasal or the rectal route. TSLP receptor deficiency negatively influenced vaccine-induced antiviral immunity by impairing the migration of dendritic cells from the airways to the draining lymph nodes of immunized mice, thereby restraining follicular helper T cell and germinal center B cell responses. As previously observed during intranasal vaccination, the adjuvant effect of IFN-λ on a rectally administered influenza vaccine was no longer observed when TSLP receptor-deficient mice were used for immunization, highlighting the central role of the IFN-λ/TSLP axis for vaccine-induced antiviral immunity in the mucosa.

Highlights

Influenza viruses cause severe respiratory disease in humans, resulting in approximately 300,000 deaths each year worldwide [1, 2]
We previously showed that Thymic stromal lymphopoietin (TSLP) can boost influenza vaccineinduced serum IgG1 titers in mice [13], but it remained unclear whether enhanced antibody titers in TSLP-treated mice would provide better protection from influenza virus-induced disease
Since previous work had shown that WT and Tslpr-/- mice display similar antibody responses after intranasal immunization with non-adjuvanted or type I IFNadjuvanted vaccines [25], these findings collectively demonstrate that functional TSLP receptors are required for optimal efficacy of IFN-l-adjuvanted mucosal vaccines

Summary

Introduction

Influenza viruses cause severe respiratory disease in humans, resulting in approximately 300,000 deaths each year worldwide [1, 2]. Vaccination with subunit vaccines can ameliorate influenza virus-induced disease, but vaccine responses are usually weak in the most vulnerable population, including the elderly [3, 4]. Recent studies indicate that viral infection can induce TSLP expression in upper airway microfold (M) cells, and that expression of TSLP correlates with viral load after influenza virus infection [11,12,13]. These results suggested that TSLP might play a role in regulating adaptive antiviral immune responses. TSLP can induce human T follicular helper (Tfh) cell differentiation and IgE production by activating DCs to express OX40 ligand [14]

Methods

Results

Conclusion