Voie d'immunisation et séquence d'administration de l ... - TEL

tel-00827710, version 1 - 29 May 2013
delivery of cell-associated antigen. As expected, i.v. immunization led to a more rapid
priming. Surprisingly, while delayed kinetically, i.d. immunization triggered a more robust
and polyfunctional primary T cell response and a better secondary response. In contrast, the
route of immunization did not impact the diversity or the avidity of the population of
responding T cells. Factors such as inflammation induced at the site of injection, subsets of
DC implicated, or persistence of antigen may all contribute to the differences observed.
To follow the characterization of the endogenous CD8 + T cell response, we were interested in
assessing the effectiveness of the combination of adjuvant with our antigen and, in particular,
focus on understanding the optimal timing for delivery, as the kinetics of antigen presentation
were dependent on the route of immunization. We demonstrated that the optimal timing of
adjuvant delivery was route of immunization-dependent and that there was an optimal time
window for adjuvant application to observe positive effects on cross-priming. We identified
some effects of poly I:C as well as type I IFN on DCs and T cells allowing us to propose a
model explaining why the timing of adjuvant delivery is crucial for optimal priming. Our
study in a fundamental model that combined antigen and adjuvant highlights multiple factors
that are important to consider when several treatments are combined. The same kind of
approaches used here in an established experimental model of cross-presentation may also be
used to compare combinatorial therapies and sequence of administration of several treatments
in complexe diseases such as cancer or chronic viral diseases.
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