title: Original encounter with antigen determines antigen-presenting cell imprinting of the quality of the immune response in mice.
abstract: BACKGROUND
  Obtaining 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.
  
  
  RESULTS
  We 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 (MPhis), 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 MPhis, 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
  This 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.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale U945, Paris, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Abadie
authors.forename: Olivia
authors.initials: O
authors.lastname: Bonduelle
authors.forename: Darragh
authors.initials: D
authors.lastname: Duffy
authors.forename: Christophe
authors.initials: C
authors.lastname: Parizot
authors.forename: Bernard
authors.initials: B
authors.lastname: Verrier
authors.forename: Béhazine
authors.initials: B
authors.lastname: Combadière
mesh_terms: D000818:Animals; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology*; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology*; D045142:Cross-Priming / Q000276:immunology; D005260:Female; D007109:Immunity / Q000276:immunology*; D007114:Immunization; D007271:Injections, Intradermal; D007273:Injections, Intramuscular; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D022423:Myeloid Cells / Q000166:cytology / Q000276:immunology; D010641:Phenotype; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D014018:Tissue Distribution / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology
chemical_list: D000941:Antigens