title: Delivering HIV Gagp24 to DCIR Induces Strong Antibody Responses In Vivo.
abstract: Targeting dendritic cell-specific endocytic receptors using monoclonal antibodies fused to desired antigens is an approach widely used in vaccine development to enhance the poor immunogenicity of protein-based vaccines and to induce immune responses. Here, we engineered an anti-human DCIR recombinant antibody, which cross-reacts with the homologous cynomolgous macaque receptor and was fused via the heavy chain C-terminus to HIV Gagp24 protein (αDCIR.Gagp24). In vitro, αDCIR.Gagp24 expanded multifunctional antigen-specific memory CD4+ T cells recognizing multiple Gagp24 peptides from HIV-infected patient peripheral blood mononuclear cells. In non human primates, priming with αDCIR.Gagp24 without adjuvant elicited a strong anti-Gagp24 antibody response after the second immunization, while in the non-targeted HIV Gagp24 protein control groups the titers were weak. The presence of the double-stranded RNA poly(I:C) adjuvant significantly enhanced the anti-Gagp24 antibody response in all the groups and reduced the discrimination between the different vaccine groups. The avidity of the anti-Gagp24 antibody responses was similar with either αDCIR.Gagp24 or Gagp24 immunization, but increased from medium to high avidity in both groups when poly(I:C) was co-administered. This data provides a comparative analysis of DC-targeted and non-targeted proteins for their capacity to induce antigen-specific antibody responses in vivo. This study supports the further development of DCIR-based DC-targeting vaccines for protective durable antibody induction, especially in the absence of adjuvant.
authors.affiliation: Baylor Institute for Immunology Research, Dallas, Texas, United States of America; Vaccine Research Institute, Créteil, France; INSERM UMR 955, Equipe 16, Créteil, France.
authors.forename: Anne-Laure
authors.initials: AL
authors.lastname: Flamar
authors.affiliation: Vaccine Research Institute, Créteil, France; CEA, Division of Immuno-Virology, IDMIT Center, Institute for Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses, France; INSERM UMR 1184, Fontenay-aux-Roses, France; Université Paris-Sud 11, Orsay, France.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Contreras
authors.affiliation: Baylor Institute for Immunology Research, Dallas, Texas, United States of America; Vaccine Research Institute, Créteil, France; INSERM UMR 955, Equipe 16, Créteil, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Zurawski
authors.affiliation: Baylor Institute for Immunology Research, Dallas, Texas, United States of America; Vaccine Research Institute, Créteil, France; INSERM UMR 955, Equipe 16, Créteil, France.
authors.forename: Monica
authors.initials: M
authors.lastname: Montes
authors.affiliation: Vaccine Research Institute, Créteil, France; CEA, Division of Immuno-Virology, IDMIT Center, Institute for Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses, France; INSERM UMR 1184, Fontenay-aux-Roses, France; Université Paris-Sud 11, Orsay, France.
authors.forename: Nathatlie
authors.initials: N
authors.lastname: Dereuddre-Bosquet
authors.affiliation: Vaccine Research Institute, Créteil, France; CEA, Division of Immuno-Virology, IDMIT Center, Institute for Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses, France; INSERM UMR 1184, Fontenay-aux-Roses, France; Université Paris-Sud 11, Orsay, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Martinon
authors.affiliation: Vaccine Research Institute, Créteil, France; INSERM UMR 955, Equipe 16, Créteil, France; Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, United States of America; Assistance Publique-Hôpitaux de Paris, Groupe Henri-Mondor Albert-Chenevier, service d'immunologie clinique, Créteil, France; Université Paris Est, Faculté de médecine, Créteil, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Banchereau
authors.affiliation: Vaccine Research Institute, Créteil, France; CEA, Division of Immuno-Virology, IDMIT Center, Institute for Emerging Diseases and Innovative Therapies, Fontenay-aux-Roses, France; INSERM UMR 1184, Fontenay-aux-Roses, France; Université Paris-Sud 11, Orsay, France.
authors.forename: Roger
authors.initials: R
authors.lastname: Le Grand
authors.affiliation: Baylor Institute for Immunology Research, Dallas, Texas, United States of America; Vaccine Research Institute, Créteil, France; INSERM UMR 955, Equipe 16, Créteil, France.
authors.forename: Gerard
authors.initials: G
authors.lastname: Zurawski
authors.affiliation: Vaccine Research Institute, Créteil, France; INSERM UMR 955, Equipe 16, Créteil, France; Assistance Publique-Hôpitaux de Paris, Groupe Henri-Mondor Albert-Chenevier, service d'immunologie clinique, Créteil, France; Université Paris Est, Faculté de médecine, Créteil, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Levy
mesh_terms: D000818:Animals; D000915:Antibody Affinity / Q000276:immunology; D000917:Antibody Formation / Q000276:immunology*; D017951:Antigen Presentation / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018984:Epitopes, T-Lymphocyte; D015483:HIV Antibodies / Q000276:immunology; D016655:HIV Core Protein p24 / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007114:Immunization; D007115:Immunization Schedule; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology*; D037181:Lectins, C-Type / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism / Q000821:virology; D008252:Macaca fascicularis; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology*; D037182:T-Cell Antigen Receptor Specificity / Q000276:immunology
chemical_list: C423004:CLEC4A protein, human; D018984:Epitopes, T-Lymphocyte; D015483:HIV Antibodies; D016655:HIV Core Protein p24; D007143:Immunoglobulin Heavy Chains; D037181:Lectins, C-Type; D008562:Membrane Glycoproteins; D011971:Receptors, Immunologic; D011993:Recombinant Fusion Proteins; C514799:p24 protein, Human Immunodeficiency Virus Type 1