Innovative approach in Pompe disease therapy: Induction of immune tolerance by antigen-encapsulated red blood cells.

Pompe disease is a glycogen storage disease caused by acid α-glucosidase enzyme deficiency. Currently, the unique treatment is lifelong enzyme replacement therapy ERT with frequent intravenous administration of the recombinant analog alglucosidase-α (AGA), which ultimately generates a sustained humoral response resulting in treatment discontinuation. Our aim is to use the tolerogenic properties of antigen-encapsulated red blood cells (RBCs) to abolish the humoral response against AGA and to restore tolerance to replacement therapy.

Red blood cells as innovative antigen carrier to induce specific immune tolerance.

The route of administration, the dose of antigen as well as the type of antigen-presenting cells (APCs) targeted are important factors to induce immune tolerance. Despite encouraging results obtained in animal models, intravenous injection of soluble antigen is unsuccessful in human clinical trials on autoimmune disease due to inefficient antigen delivery. To improve antigen delivery, we used mouse red blood cells (RBCs) as antigen vehicles to specifically target APCs which are responsible for removal of senescent RBCs after phagocytosis.

Tumor growth control using red blood cells as the antigen delivery system and poly(I:C).

The goal of most current vaccines in tumor immunology is to induce an efficient immune response against the tumor cells. The use of red blood cells (RBCs) for the delivery of tumor-associated antigen to antigen-presenting cells is an innovative approach for cancer immunotherapy. The induction of antigen-specific immune responses after administration of antigen-loaded RBCs has been demonstrated previously in mice.

Sublingual immunization with an HIV subunit vaccine induces antibodies and cytotoxic T cells in the mouse female genital tract.

A vaccine against heterosexual transmission by human immunodeficiency virus (HIV) should generate cytotoxic and antibody responses in the female genital tract and in extra-genital organs. We report that sublingual immunization with HIV-1 gp41 and a reverse transcriptase polypeptide coupled to the cholera toxin B subunit (CTB) induced gp41-specific IgA antibodies and antibody-secreting cells, as well as reverse transcriptase-specific CD8 T cells in the genital mucosa, contrary to intradermal immunization. Conjugation of the reverse transcriptase peptide to CTB favored its cross-presentation by human dendritic cells to a T cell line from an HIV(+) patient.

In situ targeting of dendritic cells by antigen-loaded red blood cells: A novel approach to cancer immunotherapy.

Red blood cells (RBCs) were shown to be efficient antigen carriers to target dendritic cells (DCs) and induce cytotoxic T-cell responses. Mouse RBCs were loaded with ovalbumin (RBC-OVA) and injected with Poly (I:C) into mice. Phagocytosis of RBC-OVA by macrophages and DCs was demonstrated to induce OVA-specific CD4(+) and CD8(+) T cell activation.

Female genital tract immunization: evaluation of candidate immunoadjuvants on epithelial cell secretion of CCL20 and dendritic/Langerhans cell maturation.

The female genital tract is an important site for numerous pathogens entry. Local immunization, generating specific mucosal IgA and systemic IgG, represents an interesting alternative immunization pathway. However, such a vaccine strategy needs mucosal adjuvants to obtain the best immune response.

Characterization of CCL20 secretion by human epithelial vaginal cells: involvement in Langerhans cell precursor attraction.

Mucosa represents the main site of pathogen/cell interactions. The two main types of cells forming the epithelial structure [epithelial cells and Langerhans cells (LC)] coordinate the first defense responses to avoid infection. To evaluate the involvement of epithelial cells in the early steps leading to a specific adaptive immune response, we have studied the interactions between vaginal epithelial and LC through the establishment of a human vaginal epithelial mucosa.