Antibody bivalency improves antiviral efficacy by inhibiting virion release independently of Fc gamma receptors

Article Article scientifique Article Antibody bivalency improves antiviral efficacy by inhibiting virion release independently of Fc gamma receptors eng 2022-02-01 author Sahin Mehmet 0000-0001-7676-3707 850445 author Remy Mélissa 0000-0003-4387-7294 712267 author Fallet Bénédict 594198 author Sommerstein Rami 672182 author Florova Marianna author Langner Anna 0000-0002-4011-9650 author Klausz Katja author Straub Tobias author Kreutzfeldt Mario 0000-0003-0335-2733 736806 author Wagner Ingrid 604950 author Schmidt Cinzia T author Malinge Pauline author Magistrelli Giovanni author Izui Shozo 25552 author Pircher Hanspeter author Verbeek J Sjef author Merkler Doron 0000-0002-0247-2007 735735 author Peipp Matthias author Pinschewer Daniel 0000-0002-1594-3189 663530 110303 10.1016/j.celrep.2022.110303 35108544 2211-1247 PMC8822495 Across the animal kingdom, multivalency discriminates antibodies from all other immunoglobulin superfamily members. The evolutionary forces conserving multivalency above other structural hallmarks of antibodies remain, however, incompletely defined. Here, we engineer monovalent either Fc-competent or -deficient antibody formats to investigate mechanisms of protection of neutralizing antibodies (nAbs) and non-neutralizing antibodies (nnAbs) in virus-infected mice. Antibody bivalency enables the tethering of virions to the infected cell surface, inhibits the release of virions in cell culture, and suppresses viral loads in vivo independently of Fc gamma receptor (FcγR) interactions. In return, monovalent antibody formats either do not inhibit virion release and fail to protect in vivo or their protective efficacy is largely FcγR dependent. Protection in mice correlates with virus-release-inhibiting activity of nAb and nnAb rather than with their neutralizing capacity. These observations provide mechanistic insights into the evolutionary conservation of antibody bivalency and help refining correlates of nnAb protection for vaccine development. Fc gamma receptors Antibody bivalency Antiviral protection Humoral immunity Immunoglobulin superfamily Inhibition of virion release Lymphocytic choriomeningitis virus (LCMV) Virus budding Virus neutralization Animals Antibodies, Neutralizing / immunology Antibodies, Neutralizing / pharmacology Antibodies, Viral / immunology Antibodies, Viral / pharmacology Antiviral Agents / pharmacology Epitopes / drug effects Epitopes / immunology HIV Antibodies / immunology HIV Antibodies / pharmacology Immunoglobulin G / drug effects Immunoglobulin G / immunology Mice, Inbred C57BL Receptors, Fc / drug effects Receptors, IgG / drug effects Receptors, IgG / immunology Dewey 616.07 Swiss National Science Foundation Immunity and tolerance in persistent viral infection 173132 CH Projects Swiss National Science Foundation Deciphering transcriptional regulators of T cell fate decisions in CNS autoimmunity 201271 CH Projects Swiss National Science Foundation Drivers and signatures of neuronal dysfunction in neuroinflammation 185321 CH Projects European Commission Molecular pathology of anti-viral T cell responses in the central nervous system 865026 PATHOCODE EU H2020 European Commission Memory B cell immunity in chronic viral infection 310962 IMMUNIBY EU FP7 137 Département de pathologie et immunologie 21F false 565 La Sclérose en plaques 908 Cell reports 38 5 46cd8a17-a650-47ef-a9b5-33f0dee53f24 Article (Published version) Public mmc2.pdf 8974991 application/pdf CC BY-4.0 7f2cf0fb-2eaf-4049-ac4d-9b0ba8193d2a Appendix Public mmc1.pdf 3134086 application/pdf Vignette Public 1-s2.0-S2211124722000158-fx1.jpg 159303 image/jpeg openAccess Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie

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Antibody bivalency improves antiviral efficacy by inhibiting virion release independently of Fc gamma receptors	Cell reports			2022	176	663

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