title: Fusion of the mouse IgG1 Fc domain to the VHH fragment (ARP1) enhances protection in a mouse model of rotavirus.
abstract: A variable fragment of a heavy chain antibody (VHH) directed against rotavirus, also referred to as anti-rotavirus protein 1 (ARP1), was shown to confer protection against rotavirus induced diarrhea in infant mouse model of rotavirus induced diarrhea. In this study, we have fused the mouse IgG1 Fc to ARP1 to improve the protective capacity of ARP1 by inducing an Fc-mediated effector function. We have shown that the Fc-ARP1 fusion protein confers significantly increased protection against rotavirus in a neonatal mouse model of rotavirus-induced diarrhea by reducing the prevalence, duration and severity of diarrhea and the viral load in the small intestines, suggesting that the Fc part of immunoglobulins may be engaged in Fc-mediated neutralization of rotavirus. Engineered conventional-like antibodies, by fusion of the Fc part of immunoglobulins to antigen-specific heavy-chain only VHH fragments, might be applied to novel antibody-based therapeutic approaches to enhance elimination of pathogens by activation of distinct effector signaling pathways.
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Immunology and Transfusion Medicine, Karolinska Institutet at Karolinska University Hospital, Huddinge, SE-14186 Stockholm, Sweden.
authors.forename: Gökçe
authors.initials: G
authors.lastname: Günaydın
authors.affiliation: Division of Protein Technology, School of Biotechnology, KTH - Royal Institute of Technology, SE-106 91, Sweden.
authors.forename: Shengze
authors.initials: S
authors.lastname: Yu
authors.affiliation: Division of Protein Technology, School of Biotechnology, KTH - Royal Institute of Technology, SE-106 91, Sweden.
authors.forename: Torbjörn
authors.initials: T
authors.lastname: Gräslund
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Immunology and Transfusion Medicine, Karolinska Institutet at Karolinska University Hospital, Huddinge, SE-14186 Stockholm, Sweden.
authors.forename: Lennart
authors.initials: L
authors.lastname: Hammarström
authors.affiliation: Department of Laboratory Medicine, Division of Clinical Immunology and Transfusion Medicine, Karolinska Institutet at Karolinska University Hospital, Huddinge, SE-14186 Stockholm, Sweden.
authors.forename: Harold
authors.initials: H
authors.lastname: Marcotte
mesh_terms: D000818:Animals; D003967:Diarrhea / Q000517:prevention & control*; D004195:Disease Models, Animal; D007074:Immunoglobulin G / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000378:metabolism; D051379:Mice; D011485:Protein Binding; D017455:Receptors, IgE / Q000378:metabolism; D012400:Rotavirus Infections / Q000517:prevention & control*; D061905:Single-Domain Antibodies / Q000378:metabolism*; D020349:Surface Plasmon Resonance
chemical_list: D007074:Immunoglobulin G; D017455:Receptors, IgE; D061905:Single-Domain Antibodies