title: Immunization route dictates cross-priming efficiency and impacts the optimal timing of adjuvant delivery.
abstract: Delivery of cell-associated antigen represents an important strategy for vaccination. While many experimental models have been developed in order to define the critical parameters for efficient cross-priming, few have utilized quantitative methods that permit the study of the endogenous repertoire. Comparing different strategies of immunization, we report that local delivery of cell-associated antigen results in delayed T cell cross-priming due to the increased time required for antigen capture and presentation. In comparison, delivery of disseminated antigen resulted in rapid T cell priming. Surprisingly, local injection of cell-associated antigen, while slower, resulted in the differentiation of a more robust, polyfunctional, effector response. We also evaluated the combination of cell-associated antigen with poly I:C delivery and observed an immunization route-specific effect regarding the optimal timing of innate immune stimulation. These studies highlight the importance of considering the timing and persistence of antigen presentation, and suggest that intradermal injection with delayed adjuvant delivery is the optimal strategy for achieving CD8⁺ T cell cross-priming.
authors.affiliation: Unité Immunobiologie des Cellules Dendritiques, Institut Pasteur Paris, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Bouvier
authors.forename: Hélène
authors.initials: H
authors.lastname: Jusforgues-Saklani
authors.forename: Annick
authors.initials: A
authors.lastname: Lim
authors.forename: Fabrice
authors.initials: F
authors.lastname: Lemaître
authors.forename: Brigitte
authors.initials: B
authors.lastname: Lemercier
authors.forename: Charlotte
authors.initials: C
authors.lastname: Auriau
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Nicola
authors.forename: Sandrine
authors.initials: S
authors.lastname: Leroy
authors.forename: Helen K
authors.initials: HK
authors.lastname: Law
authors.forename: Antonio
authors.initials: A
authors.lastname: Bandeira
authors.forename: James J
authors.initials: JJ
authors.lastname: Moon
authors.forename: Philippe
authors.initials: P
authors.lastname: Bousso
authors.forename: Matthew L
authors.initials: ML
authors.lastname: Albert