Clinical validation of IFNγ/IL-10 and IFNγ/IL-2 FluoroSpot assays for the detection of Tr1 T cells and influenza vaccine monitoring in humans

Chauvat, Anne; Benhamouda, Nadine; Gey, Alain; Lemoine, François M.; Paulie, Staffan; Carrat, Fabrice; Gougeon, Marie‐Lise; Rozenberg, Flore; Krivine, Anne; Cheraï, Mustapha; Lehmann, Paul; Quintin-Colonna, Françoise; Launay, Odile; Tartour, Éric

doi:10.4161/hv.26593

Cited by 18 publications

(13 citation statements)

References 71 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Characterization of the anti-E75 specific CD8 (34). The E75 peptide vaccine was used at 50-fold higher molar concentrations than STxB-E75, as no induction of specific CD8 þ T cells was observed at low E75 peptide concentrations (Fig.…”

Section: Resultsmentioning

confidence: 99%

A Therapeutic Her2/neu Vaccine Targeting Dendritic Cells Preferentially Inhibits the Growth of Low Her2/neu–Expressing Tumor in HLA-A2 Transgenic Mice

Tran

Diniz

Dransart

et al. 2016

Clinical Cancer Research

Self Cite

View full text Add to dashboard Cite

Purpose: E75, a peptide derived from the Her2/neu protein, is the most clinically advanced vaccine approach against breast cancer. In this study, we aimed to optimize the E75 vaccine using a delivery vector targeting dendritic cells, the B-subunit of Shiga toxin (STxB), and to assess the role of various parameters (Her2/neu expression, combination with trastuzumab) in the efficacy of this cancer vaccine in a relevant preclinical model.Experimental Design: We compared the differential ability of the free E75 peptide or the STxB-E75 vaccine to elicit CD8 þ T cells, and the impact of the vaccine on murine HLA-A2 tumors expressing low or high levels of Her2/neu. Results: STxB-E75 synergized with granulocyte macrophage colony-stimulating factors and CpG and proved to be more efficient than the free E75 peptide in the induction of multifunctional and high-avidity E75-specific anti-CD8 þ T cells resulting in a potent tumor protection in HLA-A2 transgenic mice. High expression of HER2/neu inhibited the expression of HLA-class I molecules, leading to a poor recognition of human or murine tumors by E75-specific cytotoxic CD8 þ T cells. In line with these results, STxB-E75 preferentially inhibited the growth of HLA-A2 tumors expressing low levels of Her2/neu. Coadministration of anti-Her2/neu mAb potentiated this effect.Conclusions: STxB-E75 vaccine is a potent candidate to be tested in patients with low Her2/neu-expressing tumors. It could also be indicated in patients expressing high levels of Her2/neu and low intratumoral T-cell infiltration to boost the recruitment of T cells-a key parameter in the efficacy of anti-Her2/neu mAb therapy.

show abstract

Section: Resultsmentioning

confidence: 99%

A Therapeutic Her2/neu Vaccine Targeting Dendritic Cells Preferentially Inhibits the Growth of Low Her2/neu–Expressing Tumor in HLA-A2 Transgenic Mice

Tran

Diniz

Dransart

et al. 2016

Clinical Cancer Research

Self Cite

View full text Add to dashboard Cite

show abstract

“…This method allows characterization of the cell secretion profile after their potential stimulation, along with their surface phenotype. However, despite precise identification of the producing cells, the sensitivity of ICS is generally lower than that of other immunoassays [78].…”

Section: Cytokine Profilingmentioning

confidence: 99%

Predictive Markers of Immunogenicity and Efficacy for Human Vaccines

et al. 2021

View full text Add to dashboard Cite

Vaccines represent one of the major advances of modern medicine. Despite the many successes of vaccination, continuous efforts to design new vaccines are needed to fight “old” pandemics, such as tuberculosis and malaria, as well as emerging pathogens, such as Zika virus and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Vaccination aims at reaching sterilizing immunity, however assessing vaccine efficacy is still challenging and underscores the need for a better understanding of immune protective responses. Identifying reliable predictive markers of immunogenicity can help to select and develop promising vaccine candidates during early preclinical studies and can lead to improved, personalized, vaccination strategies. A systems biology approach is increasingly being adopted to address these major challenges using multiple high-dimensional technologies combined with in silico models. Although the goal is to develop predictive models of vaccine efficacy in humans, applying this approach to animal models empowers basic and translational vaccine research. In this review, we provide an overview of vaccine immune signatures in preclinical models, as well as in target human populations. We also discuss high-throughput technologies used to probe vaccine-induced responses, along with data analysis and computational methodologies applied to the predictive modeling of vaccine efficacy.

show abstract

“…The FluoroSpot assay was described previously (33,34). Briefly, PBMCs were cultured for 7 d at 2 3 10 6 cells/ml in 2 ml/well pool of CCNB1 peptides (individual peptides at a concentration of 5 mg/ml) complete RPMI 1640 medium supplemented with 5% serum AB.…”

Section: Assessment Of Ccnb1-specific Cd4 + T Cell Responses By Fluormentioning

confidence: 99%

The Tumor Antigen Cyclin B1 Hosts Multiple CD4 T Cell Epitopes Differently Recognized by Pre-Existing Naive and Memory Cells in Both Healthy and Cancer Donors

Chevaleyre

Benhamouda

Favry

et al. 2015

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

Cyclin B1 (CCNB1) is considered as a potential target for a cancer vaccine, as it is overexpressed in many malignant cells, while being transiently expressed in normal cells. To evaluate the CD4 T cell response to CCNB1, we derived T cell lines by multiple weekly rounds of stimulation with recombinant CCNB1 of T cells collected in healthy donors (long-term T cell assays). T cell lines were specific for 15 immunodominant peptides and derived preferentially from naive T cells. From 74 overlapping peptides, 20 peptides were selected for their broad specificity of binding to HLA class II molecules and included most of the immunodominant epitopes. They primed in vitro a large number of specific CD4 T cell lines in all the donors. Immunodominant epitopes were the most efficacious in long-term T cell assays, both in terms of number of specific T cell lines and number of responding donors. The 20 peptides were also submitted to short-term T cell assays using cells collected in healthy and cancer patients with the aim to evaluate the memory response. The recognized peptides differed from the immunodominant peptides and were part of the best promiscuous peptides. We also observed pre-existing CCNB1-specifc IgG Abs in both healthy and cancer donors. Long- and short-term T cell assays revealed that CCNB1 contained many CD4 T cell epitopes, which are differentially recognized by pre-existing naive and memory CD4 T cells. These observations are of value for the design of cancer vaccines.

show abstract

Clinical validation of IFNγ/IL-10 and IFNγ/IL-2 FluoroSpot assays for the detection of Tr1 T cells and influenza vaccine monitoring in humans

Cited by 18 publications

References 71 publications

A Therapeutic Her2/neu Vaccine Targeting Dendritic Cells Preferentially Inhibits the Growth of Low Her2/neu–Expressing Tumor in HLA-A2 Transgenic Mice

A Therapeutic Her2/neu Vaccine Targeting Dendritic Cells Preferentially Inhibits the Growth of Low Her2/neu–Expressing Tumor in HLA-A2 Transgenic Mice

Predictive Markers of Immunogenicity and Efficacy for Human Vaccines

The Tumor Antigen Cyclin B1 Hosts Multiple CD4 T Cell Epitopes Differently Recognized by Pre-Existing Naive and Memory Cells in Both Healthy and Cancer Donors

Contact Info

Product

Resources

About