title: Secretory IgA as a vaccine carrier for delivery of HIV antigen to M cells.
abstract: HIV transmission and spread in the host are based on the survival of the virus or infected cells present in mucosal secretions, and the virus' ability to cross the epithelial barrier and access immune target cells, which leads to systemic infection. Therefore, HIV-specific immunity at mucosal sites is critical for control of infection. Although mucosal delivery would ensure the best onset of protective immunity, most candidate vaccines are administered through the parenteral route. Remarkably, secretory IgA (SIgA) interacts specifically with mucosal microfold (M) cells present in gut-associated lymphoid tissues. Here we evaluate the feasibility of delivering chemically bound p24HIV antigen via SIgA into the intestinal mucosae in mice. After oral administration, p24-SIgA complexes are quickly delivered into the tissue and selectively captured by CX3CR1(+) dendritic cells. Oral immunization with p24gag linked to SIgA (p24-SIgA) adjuvanted with E. coli heat labile enterotoxin (HLT) elicits both humoral and cellular immune responses against p24 at the systemic and mucosal levels and induces efficient protection against rectal challenge with a recombinant vaccinia virus encoding gag. This is the first study which underscores the remarkable potential of SIgA to serve as a vaccine carrier for an HIV antigen in mucosal administration targeting the gastrointestinal environment.
authors.affiliation: GIMAP/EA3064, Université de Lyon, CIC CIE3 Vaccinology, Saint-Etienne, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Rochereau
authors.forename: Vincent
authors.initials: V
authors.lastname: Pavot
authors.forename: Bernard
authors.initials: B
authors.lastname: Verrier
authors.forename: Agathe
authors.initials: A
authors.lastname: Ensinas
authors.forename: Christian
authors.initials: C
authors.lastname: Genin
authors.forename: Blaise
authors.initials: B
authors.lastname: Corthésy
authors.forename: Stéphane
authors.initials: S
authors.lastname: Paul
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology / Q000494:pharmacology*; D000818:Animals; D004337:Drug Carriers / Q000494:pharmacology*; D016655:HIV Core Protein p24 / Q000276:immunology / Q000494:pharmacology*; D015497:HIV-1 / Q000276:immunology*; D007111:Immunity, Cellular / Q000187:drug effects; D056724:Immunity, Humoral / Q000187:drug effects; D007071:Immunoglobulin A, Secretory / Q000276:immunology / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic
chemical_list: D016915:AIDS Vaccines; D004337:Drug Carriers; D016655:HIV Core Protein p24; D007071:Immunoglobulin A, Secretory; C514799:p24 protein, Human Immunodeficiency Virus Type 1
keywords: HIV vaccine strategy; Microfold cells; Oral vaccination; SIgA reverse transcytosis