Abstract EN:

Immune protection against viral respiratory infections requires the induction of synchronized innate and adaptive immune responses. In this thesis, the role of various immune effectors acting in the early and late phases of the immune responses after infection and vaccination was studied. A murine model of vaccinia virus nasal infection allowed us to establish the pivotal role of myeloid dendritic cells expressing the CX3CR1 chemokine receptor in the initiation of specific T cell response. These results demonstrate the existence of an early coordination between innate and adaptive arms of the immune system, which is involved in the induction of a protective response. Data from two clinical studies were used to study various immune parameters after vaccination and infection with pandemic A(H1N1)pdm09 influenza virus and to model the induced responses. A multiparametric analysis of seven effectors of the adaptive immunity shows strong heterogeneity of vaccine-induced immune responses, depending on the residual anti-influenza response. A principal component analysis identifies five profiles of adaptive responses. In addition, a year after vaccination, specific immune memory has similar characteristics to the induced responses detected after a moderate viral infection. However, the quality and intensity of memory responses after pandemic vaccine are different from the one observed after a severe infection with A(H1N1)pdm09 influenza virus. These results suggest that a balance between the different compartments of the cellular immune responses after vaccination or infection is essential for immune protection. This work opens up new ways in the correlates of vaccine efficacy and protection.