Early Transcriptome Signatures from Immunized Mouse Dendritic Cells Predict Late Vaccine-Induced T-Cell Responses

Systems biology offers promising approaches for identifying response-specific signatures to vaccination and assessing their predictive value. Here, we designed a modelling strategy aiming to predict the quality of late T-cell responses after vaccination from early transcriptome analysis of dendritic cells. Using standardized staining with tetramer, we first quantified antigen-specific T-cell expansion 5 to 10 days after vaccination with one of a set of 41 different vaccine vectors all expressing the same antigen. Hierarchical clustering of the responses defined sets of high and low T cell response inducers. We then compared these responses with the transcriptome of splenic dendritic cells obtained 6 hours after vaccination with the same vectors and produced a random forest model capable of predicting the quality of the later antigen-specific T-cell expansion. The model also successfully predicted vector classification as low or strong T-cell response inducers of a novel set of vaccine vectors, based on the early transcriptome results obtained from spleen dendritic cells, whole spleen and even peripheral blood mononuclear cells. Finally, our model developed with mouse datasets also accurately predicted vaccine efficacy from literature-mined human datasets.Author Summary: Vaccines are designed to elicit effective immune responses against antigens. The various vector platforms used in vaccine development are diverse and complex, rendering the selection of promising vaccines vector challenging. We have designed a modeling strategy that predicts the propensity of vaccine vectors to elicit strong late T-cell responses using transcriptome material obtained 6 hours after vaccination. Our model, designed with mouse datasets, also predicted vector efficacy from mined human data. Thus, molecular signatures obtained 6 hours after vaccination can predict vaccine efficacy at 2 weeks post vaccination, which should help in vaccine development.