Original Research ARTICLE
Immunization route dictates cross-priming efficiency and impacts the optimal timing of adjuvant delivery
- 1 Unité Immunobiologie des Cellules Dendritiques, Institut Pasteur, Paris, France
- 2 INSERM U818, Paris, France
- 3 Unité de Régulation Immunitaire et Vaccinologie, Institut Pasteur, Paris, France
- 4 Unité Dynamique des Réponses Immunes, Institut Pasteur, Paris, France
- 5 INSERM U668, Paris, France
- 6 Imagopole, Plate-Forme d’Imagerie Dynamique, Institut Pasteur, Paris, France
- 7 Unité Epidémiologie des Maladies Emergentes, Institut Pasteur, Paris, France
- 8 Centre for Human Immunology, Institut Pasteur, Paris, France
- 9 Unité Biologie des Populations Lymphocytaires, Institut Pasteur, Paris, France
- 10 Department of Microbiology and Center for Immunology, University of Minnesota Medical School, Minneapolis, USA
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.
Keywords: dentritic cells, cross-priming, polyfunctional T cells, adjuvant delivery
Citation: Bouvier I, Jusforgues-Saklani H, Lim A, Lemaître F, Lemercier B, Auriau C, Nicola M-A, Leroy S, Law HK, Bandeira A, Moon JJ, Bousso P and Albert ML (2011) Immunization route dictates cross-priming efficiency and impacts the optimal timing of adjuvant delivery. Front. Immun. 2:71. doi: 10.3389/fimmu.2011.00071
Received: 05 October 2011;
Accepted: 17 November 2011;
Published online: 08 December 2011.
Edited by:Ken J. Ishii, National Institute of Biomedical Innovation, Japan
Copyright: © 2011 Bouvier, Jusforgues-Saklani, Lim, Lemaître, Lemercier, Auriau, Nicola, Leroy, Law, Bandeira, Moon, Bousso and Albert. This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
*Correspondence: Matthew L. Albert, Institut Pasteur, 25, Rue du Dr. Roux, Paris 75724, France. e-mail: firstname.lastname@example.org
†Present address: James J. Moon, Center for Immunology and Inflammatory Diseases, and Pulmonary and Critical Care Unit, Massachusetts General Hospital; and Harvard Medical School, 149 13th Street, Charlestown, MA 02129. USA.