Vaccine-Induced Th17 Cells Are Maintained Long-Term Postvaccination as a Distinct and Phenotypically Stable Memory Subset

Abstract

Th17 cells are increasingly being recognized as an important T helper subset for immune-mediated protection, especially against pathogens at mucosal ports of entry. In several cases, it would thus be highly relevant to induce Th17 memory by vaccination. Th17 cells are reported to exhibit high plasticity and may not stably maintain their differentiation program once induced, questioning the possibility of inducing durable Th17 memory. Accordingly, there is no consensus as to whether Th17 memory can be established unless influenced by continuous Th17 polarizing conditions. We have previously reported (T. Lindenstrøm, et al., J. Immunol. 182:8047-8055, 2009) that the cationic liposome adjuvant CAF01 can prime both Th1 and Th17 responses and promote robust, long-lived Th1 memory. Here, we demonstrate that subunit vaccination in mice with CAF01 leads to establishment of bona fide Th17 memory cells. Accordingly, Th17 memory cells exhibited lineage stability by retaining both phenotypic and functional properties for nearly 2 years. Antigen-specific, long-term Th17 memory cells were found to be mobilized from lungdraining lymph nodes to the lung following an aerosol challenge by Mycobacterium tuberculosis nearly 2 years after their induction and proliferated at levels comparable to those of Th1 memory cells. During the infection, the vaccine-induced Th17 memory cells expanded in the lungs and adapted Th1 characteristics, implying that they represent a metastable population which exhibits plasticity when exposed to prolonged Th1 polarizing, inflammatory conditions such as those found in the M. tuberculosis-infected lung. In the absence of overt inflammation, however, stable bona fide Th17 memory can indeed be induced by parenteral immunization.

Characterization and Optimization of the Glucan Particle-Based Vaccine Platform

“…These data suggest that long-term Th1 and Th17 memory responses are induced using the GP platform. Although there is controversy regarding the longevity of Th17 cells, our results are consistent with a recent study showing long-lasting Th1 and Th17 memory cells following subunit vaccination with antigens administered with the cationic liposome adjuvant CAF01 (19). Interestingly, in both our study and the aforementioned study, a small but distinctive population of IFN-␥/IL-17A double-positive antigen-specific CD4 ϩ T cells was detected.…”

Novel Vaccination Strategies against Tuberculosis

“…This liposome-based formulation combines the cationic surfactant dimethyldioctadecylammonium (DDC) with trehalose-dibehenate (TDB), a synthetic analog of the mycobacterial cord factor. This adjuvant signals through the innate immune receptor monocyte-inducible C-type lectin (Mincle) and has strong adjuvant properties comprising long-lived memory Th1 and Th17 responses (Lindenstrom et al 2009(Lindenstrom et al , 2012Desel et al 2013) in adult as well as in neonatal mice (Kamath et al 2009). The CAF01 adjuvant combined with the H1 molecule has recently successfully completed a clinical phase I trial.…”

Low Antigen Dose in Adjuvant-Based Vaccination Selectively Induces CD4 T Cells with Enhanced Functional Avidity and Protective Efficacy

“…This discrepancy could be related to the differences in the experimental setups, adjuvants (CFA versus CAF09), and readout (MHC-multimer stain versus functional assay) used. CAF09 and related CAF adjuvants were shown to imprint effector and central memory phenotypes, as well as Th lineage choice, early after the first or second immunization, and these imprinted phenotypes are stable over prolonged periods of time, even during the course of infection (47)(48)(49). This might indicate stable epigenetic regulation of T cell phenotype, as well as functional avidity, which was already imprinted after the first immunization with CAF09.…”