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

tel-00827710, version 1 - 29 May 2013
In instances where microbial associated molecular patterns are absent (e.g., cell-associated
antigen), it is common practice to formulate the vaccine with an adjuvant. While adjuvants
have been shown to be useful for enhancing the response to antigen, it has also been observed
that DC maturation prior to immunization can have the opposite effect – the inhibition of
subsequent T cell priming (Wilson et al., 2006). Following from our results indicating
delayed cross-presentation after i.d. immunization (Figure 32), we predicted that the optimal
timing of adjuvant delivery will depend on the route of immunization.
I. THE OPTIMAL TIMING FOR ADJUVANT DELIVERY IS
DEPENDENT ON THE ROUTE OF IMMUNIZATION
Our prediction was that the optimal timing for adjuvant delivery may be earlier for i.v.
immunization as compared to i.d. immunization, due to the different kinetic of cross-
presentation observed in Figure 32. To test this, mice were again immunized with K bm1 mOva
splenocytes i.d. or i.v. Poly I:C was used as an adjuvant and administered at different time
points relative to immunization with antigen. The absolute number of antigen-specific T cells
was determined at the respective time of peak response (day 7 for i.v. and day 9 for i.d.
immunization). When poly I:C was injected one day prior, or the day of i.v. immunization
with the K bm1 mOva cells, T cell priming was greatly reduced (Figure 37A). Strikingly,
injection of poly I:C one day after i.v. immunization enhanced T cell priming. For the i.d.
route, poly I:C injection one day prior to, the day of, or even one day after immunization,
resulted in the inhibition of T cell priming (Figure 37B). It was necessary to wait until three
days post-immunization to inject poly I:C in order to observe an enhancement of T cell
priming (Figure 37B). Following from the results presented in Figure 32, we suggest that
antigen capture has to occur prior to adjuvant detection by DCs and that one day of antigen
capture is sufficient to permit T cell priming after i.v. immunization, but that additional time
is required for antigen capture after i.d. immunization. This hypothesis could explain why
delayed adjuvant delivery is optimal for i.d. immunization.
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