title: Delivery of antigen to nasal-associated lymphoid tissue microfold cells through secretory IgA targeting local dendritic cells confers protective immunity.
abstract: BACKGROUND
  Transmission of mucosal pathogens relies on their ability to bind to the surfaces of epithelial cells, to cross this thin barrier, and to gain access to target cells and tissues, leading to systemic infection. This implies that pathogen-specific immunity at mucosal sites is critical for the control of infectious agents using these routes to enter the body. Although mucosal delivery would ensure the best onset of protective immunity, most of the candidate vaccines are administered through the parenteral route.
  
  
  OBJECTIVE
  The present study evaluates the feasibility of delivering the chemically bound p24gag (referred to as p24 in the text) HIV antigen through secretory IgA (SIgA) in nasal mucosae in mice.
  
  
  RESULTS
  We show that SIgA interacts specifically with mucosal microfold cells present in the nasal-associated lymphoid tissue. p24-SIgA complexes are quickly taken up in the nasal cavity and selectively engulfed by mucosal dendritic cell-specific intercellular adhesion molecule 3-grabbing nonintegrin-positive dendritic cells. Nasal immunization with p24-SIgA elicits both a strong humoral and cellular immune response against p24 at the systemic and mucosal levels. This ensures effective protection against intranasal challenge with recombinant vaccinia virus encoding p24.
  
  
  CONCLUSIONS
  This study represents the first example that underscores the remarkable potential of SIgA to serve as a carrier for a protein antigen in a mucosal vaccine approach targeting the nasal environment.
authors.affiliation: GIMAP/EA3064, Université de Lyon, CIC 1408 Vaccinology, Saint-Etienne, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rochereau
authors.affiliation: Institut de Biologie & Chimie des Protéines - LBTI, UMR 5305 - CNRS/University of Lyon, Lyon, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Pavot
authors.affiliation: Institut de Biologie & Chimie des Protéines - LBTI, UMR 5305 - CNRS/University of Lyon, Lyon, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Verrier
authors.affiliation: GIMAP/EA3064, Université de Lyon, CIC 1408 Vaccinology, Saint-Etienne, France.
authors.forename: Fabienne
authors.initials: F
authors.lastname: Jospin
authors.affiliation: GIMAP/EA3064, Université de Lyon, CIC 1408 Vaccinology, Saint-Etienne, France.
authors.forename: Agathe
authors.initials: A
authors.lastname: Ensinas
authors.affiliation: GIMAP/EA3064, Université de Lyon, CIC 1408 Vaccinology, Saint-Etienne, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Genin
authors.affiliation: R&D Laboratory of the Division of Immunology and Allergy, CHUV, Centre des Laboratoires d'Epalinges, Epalinges, Switzerland.
authors.forename: Blaise
authors.initials: B
authors.lastname: Corthésy
authors.affiliation: GIMAP/EA3064, Université de Lyon, CIC 1408 Vaccinology, Saint-Etienne, France. Electronic address: stephane.paul@chu-st-etienne.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Paul
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D016207:Cytokines / Q000276:immunology; D003713:Dendritic Cells; D005260:Female; D016655:HIV Core Protein p24 / Q000276:immunology*; D018928:Immunity, Mucosal; D007114:Immunization / Q000379:methods*; D007070:Immunoglobulin A / Q000276:immunology; D007071:Immunoglobulin A, Secretory / Q000276:immunology*; D007074:Immunoglobulin G / Q000276:immunology; D008221:Lymphoid Tissue / Q000166:cytology / Q000276:immunology*; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009297:Nasal Mucosa / Q000166:cytology / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D014621:Vagina / Q000276:immunology
chemical_list: D016207:Cytokines; D016655:HIV Core Protein p24; D007070:Immunoglobulin A; D007071:Immunoglobulin A, Secretory; D007074:Immunoglobulin G
keywords: Nasal vaccine strategy; microfold cells; nasal-associated lymphoid tissue; protection; reverse transcytosis; secretory IgA