title: The immune complex CTA1-DD/IgG adjuvant specifically targets connective tissue mast cells through FcγRIIIA and augments anti-HPV immunity after nasal immunization.
abstract: We have previously reported that CTA1-DD/IgG immune complexes augment antibody responses in a mast cell-dependent manner following intranasal (IN) immunizations. However, from a safety perspective, mast cell activation could preclude clinical use. Therefore, we have extended these studies and demonstrate that CTA1-DD/IgG immune complexes administered IN did not trigger an anaphylactic reaction. Importantly, CTA1-DD/IgE immune complexes did not activate mast cells. Interestingly, only connective tissue, but not mucosal, mast cells could be activated by CTA1-DD/IgG immune complexes. This effect was mediated by FcγRIIIA, only expressed on connective tissue mast cells, and found in the nasal submucosa. FcγRIIIA-deficient mice had compromised responses to immunization adjuvanted by CTA1-DD/IgG. Proof-of-concept studies revealed that IN immunized mice with human papillomavirus (HPV) type 16 L1 virus-like particles (VLP) and CTA1-DD/IgG immune complexes demonstrated strong and sustained specific antibody titers in serum and vaginal secretions. From a mast cell perspective, CTA1-DD/IgG immune complexes appear to be safe and effective mucosal adjuvants.
authors.affiliation: 1] Department of Microbiology and Immunology, Mucosal Immunobiology and Vaccine Research Center, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden [2] Department of Microbiology and Immunology, Affiliated Hospital of Guiyang Medical College, Guiyang, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Fang
authors.forename: T
authors.initials: T
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Lidell
authors.forename: X
authors.initials: X
authors.lastname: Xu
authors.forename: N
authors.initials: N
authors.lastname: Lycke
authors.forename: Z
authors.initials: Z
authors.lastname: Xiang
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage*; D000281:Administration, Intranasal; D000818:Animals; D000914:Antibodies, Viral / Q000378:metabolism; D000917:Antibody Formation / Q000187:drug effects; D015550:Cell Degranulation / Q000187:drug effects; D002460:Cell Line; D002772:Cholera Toxin / Q000008:administration & dosage*; D003238:Connective Tissue / Q000473:pathology*; D006801:Humans; D008407:Mast Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009297:Nasal Mucosa / Q000378:metabolism* / Q000473:pathology; D027383:Papillomaviridae / Q000276:immunology*; D030361:Papillomavirus Infections / Q000276:immunology*; D017452:Receptors, IgG / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D014765:Viral Vaccines
chemical_list: D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; C440610:CTA1-DD protein, recombinant; C517507:FcgammaRIIIA protein, mouse; D017452:Receptors, IgG; D011993:Recombinant Fusion Proteins; D014765:Viral Vaccines; D002772:Cholera Toxin