Original Encounter with Antigen Determines Antigen-Presenting Cell Imprinting of the Quality of the Immune Response in Mice |
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Authors: | Valérie Abadie Olivia Bonduelle Darragh Duffy Christophe Parizot Bernard Verrier Béhazine Combadière |
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Institution: | 1. Institut National de la Santé et de la Recherche Médicale (INSERM) U945, Paris, France.; 2. University of Pierre and Marie Curie (UPMC)- Univ Paris 06, Paris, France.; 3. Assistance-Publique/Hopitaux-de-Paris, Immunity and Infection, Paris, France.; 4. Institut de Biologie et Chimie des Protéines, UMR 5086 CNRS/UCBL, Lyon, France.;New York University School of Medicine, United States of America |
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Abstract: | BackgroundObtaining a certain multi-functionality of cellular immunity for the control of infectious diseases is a burning question in immunology and in vaccine design. Early events, including antigen shuttling to secondary lymphoid organs and recruitment of innate immune cells for adaptive immune response, determine host responsiveness to antigens. However, the sequence of these events and their impact on the quality of the immune response remain to be elucidated. Here, we chose to study Modified Vaccinia virus Ankara (MVA) which is now replacing live Smallpox vaccines and is proposed as an attenuated vector for vaccination strategies against infectious diseases.Methodology/Principal findingsWe analyzed in vivo mechanisms triggered following intradermal (i.d.) and intramuscular (i.m.) Modified Vaccinia virus Ankara (MVA) administration. We demonstrated significant differences in the antigen shuttling to lymphoid organs by macrophages (MΦs), myeloid dendritic cells (DCs), and neutrophils (PMNs). MVA i.d. administration resulted in better antigen distribution and more sustained antigen-presenting cells (APCs) recruitment into draining lymph nodes than with i.m. administration. These APCs, which comprise both DCs and MΦs, were differentially involved in T cell priming and shaped remarkably the quality of cytokine-producing virus-specific T cells according to the entry route of MVA.Conclusions/SignificanceThis study improves our understanding of the mechanisms of antigen delivery and their consequences on the quality of immune responses and provides new insights for vaccine development. |
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