Team Leader :
Combadière BehazineContact the team
Vaccine efficacy is a major public health issue for protection against infectious diseases. Vaccinology is a multidisciplinary field that is now progressing towards the discovery of early biomarkers of vaccine efficacy in order to accelerate vaccine development. Humoral responses are considered as markers of efficacy of immune responses for protection but these responses are detected months after vaccination. However, immune responses to vaccines are heterogeneous and variable among individuals. This heterogeneity is due to several factors: 1) genetic factors, 2) factors related to the individual (immunological history, microbiota, obesity, age, chronic diseases, allergies etc.) and 3) the vaccination strategy (formulation, number of doses, injection site etc.). We are studying the impact of these last two factors on vaccine responsiveness.
The search for early biomarkers (hours/days after vaccination) is a key issue to predict the degree of vaccine efficacy that will 1) allow to rapidly refine vaccination strategies; 2) help to select at early stages several vaccine candidates and, finally 3) advance in the understanding of the complex biological pathways involved in the initiation of adaptive immunity.
We have recently demonstrated the major impact of the gene expression signature in blood before or 1 day after vaccine administration on the quality of adaptive immunity (humoral cells versus CD8 cytotoxic cells). Our objectives are to use biological data generated during clinical studies of several vaccines to propose mechanistic hypotheses and to identify candidate biomarkers of vaccine immunological efficacy.
Keywords : Immune mechanism – Transcriptome – Adaptive immunity – Biomarkers – Multiparametric cytometry (Spectral, cytof) – Innate immunity
Our research focus on 2 axes
1. Generate and consolidate biological data after vaccination.
The objective is to study molecular and cellular immune networks in blood after vaccination (vaccines targeting HIV, Covid19, seasonal influenza) and determine their role in the induction of adaptive responses using systems biology approaches in human clinical trials. The program relies on a unique collection of data that will lead to the discovery of biomarkers as well as methodological approaches based on several clinical studies (2016-2022) in collaboration with national and European partners (H2020 project, FRM, Eurostars, BPI France).
2. Interpreting the early innate immune signature for the discovery of the mechanisms of the vaccine-induced immune response.
The objective is to increase our basic knowledge of innate immunity, which could predict the expected immune responses in most individuals after vaccination. We aim to find cellular and molecular biomarkers (data collected in axis 1) that dictate biological outcomes related to protection against infections. We use preclinical models to study the initial immune mechanisms linking early immunity to long-term protection against infection. This research program will accelerate vaccine development and measurement of its immune efficacy.
- Immune mechanisms
- Systems vaccinology
- Biomarkers of vaccine immune efficacy
- Phase I/II clinical studies
- Preclinical murine models