title: Broadly neutralizing antibodies suppress post-transcytosis HIV-1 infectivity.
abstract: Broadly neutralizing antibodies (bNAbs) offer promising opportunities for preventing HIV-1 infection in humans. Immunoprophylaxis with potent bNAbs efficiently protects non-human primates from mucosal transmission even after repeated challenges. However, the precise mechanisms of bNAb-mediated viral inhibition in mucosal tissues are currently unknown. Here, we show that immunoglobulin (Ig)G and IgA bNAbs do not interfere with the endocytic transport of HIV-1 across epithelial cells, a process referred to as transcytosis. Instead, both viruses and antibodies are translocated to the basal pole of epithelial cells, possibly in the form of an immune complex. Importantly, as opposed to free virions, viral particles bound by bNAbs are no longer infectious after transepithelial transit. Post-transcytosis neutralization activity of bNAbs displays comparable inhibitory concentrations as those measured in classical neutralization assays. Thus, bNAbs do not block the transport of incoming HIV-1 viruses across the mucosal epithelium but rather neutralize the transcytosed virions, highlighting their efficient prophylactic and protective activity in vivo.
authors.affiliation: Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris, France.|INSERM U1222, Paris, France.|Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: V
authors.initials: V
authors.lastname: Lorin
authors.affiliation: Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris, France.|INSERM U1222, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Malbec
authors.affiliation: Laboratory of Molecular Immunology, The Rockefeller University, New York City, New York, USA.|Icahn School of Medicine at Mount Sinai, New York City, New York, USA.
authors.forename: C
authors.initials: C
authors.lastname: Eden
authors.affiliation: Virus & Immunity Unit, Department of Virology, Institut Pasteur, Paris, France.|CNRS URA3015, Paris, France.|Vaccine Research Institute, Créteil, France.
authors.forename: T
authors.initials: T
authors.lastname: Bruel
authors.affiliation: Virus & Immunity Unit, Department of Virology, Institut Pasteur, Paris, France.|CNRS URA3015, Paris, France.
authors.forename: F
authors.initials: F
authors.lastname: Porrot
authors.affiliation: Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
authors.forename: M S
authors.initials: MS
authors.lastname: Seaman
authors.affiliation: Virus & Immunity Unit, Department of Virology, Institut Pasteur, Paris, France.|CNRS URA3015, Paris, France.|Vaccine Research Institute, Créteil, France.
authors.forename: O
authors.initials: O
authors.lastname: Schwartz
authors.affiliation: Laboratory of Humoral Response to Pathogens, Department of Immunology, Institut Pasteur, Paris, France.|INSERM U1222, Paris, France.|Vaccine Research Institute, Créteil, France.
authors.forename: H
authors.initials: H
authors.lastname: Mouquet
mesh_terms: D016915:AIDS Vaccines / Q000276:immunology*; D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D002478:Cells, Cultured; D003429:Cross Reactions; D004847:Epithelial Cells / Q000276:immunology* / Q000821:virology; D015483:HIV Antibodies / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007070:Immunoglobulin A / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D011323:Primates; D057900:Transcytosis; D014771:Virion / Q000378:metabolism*; D014774:Virulence
chemical_list: D016915:AIDS Vaccines; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015488:HIV Antigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G