title: Neutralizing monoclonal antibodies to human immunodeficiency virus type 1 do not inhibit viral transcytosis through mucosal epithelial cells.
abstract: HIV-1 transcytosis has been proposed as a potential mechanism allowing the virus to cross the epithelium during mucosal transmission. Epitopes of the HIV-1 envelope involved in this process have not been identified yet. Here, we assessed a large panel of HIV neutralizing antibodies recognizing well-characterized epitopes of the HIV-1 envelope for their ability to block HIV-1 transcytosis across a confluent epithelial monolayer. We found that all of the 13 HIV-1-specific monoclonal antibodies tested in the present study, including the three broadly neutralizing antibodies 2F5, 2G12 and IgG1b12, lacked the ability to inhibit transcytosis of cell-free and cell-associated R5- as X4-tropic HIV-1 across a tight and polarized monolayer of HEC-1 epithelial cells. In contrast, anti-gp160 polyclonal antibodies purified from serum or breast milk of HIV-1-infected individuals potently inhibited HIV-1 transcytosis. Furthermore, polymeric S-IgA exhibited similar ability to inhibit transcytosis compared to IgG despite their lower anti-gp160 specific activity. Together, these results demonstrate that the major neutralizing envelope epitopes of HIV-1 are not involved in HIV-1 transcytosis, and suggest that surface agglutination of virus particles may participate to the blocking effect observed with both polyclonal and polymeric anti-gp160 immunoglobulins.
authors.affiliation: Université Paris V, et Unité Internationale INSERM 743 (Immunologie Humaine), Equipe Immunité et Biothérapie Muqueuse, Centre de Recherches Biomédicales des Cordeliers, Paris, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chomont
authors.forename: Hakim
authors.initials: H
authors.lastname: Hocini
authors.forename: Jean-Chrysostome
authors.initials: JC
authors.lastname: Gody
authors.forename: Hicham
authors.initials: H
authors.lastname: Bouhlal
authors.forename: Pierre
authors.initials: P
authors.lastname: Becquart
authors.forename: Corinne
authors.initials: C
authors.lastname: Krief-Bouillet
authors.forename: Michel
authors.initials: M
authors.lastname: Kazatchkine
authors.forename: Laurent
authors.initials: L
authors.lastname: Bélec
mesh_terms: D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002460:Cell Line; D004847:Epithelial Cells / Q000276:immunology / Q000821:virology; D005260:Female; D015483:HIV Antibodies / Q000494:pharmacology*; D019302:HIV Envelope Protein gp160 / Q000276:immunology; D015658:HIV Infections / Q000276:immunology / Q000635:transmission / Q000821:virology; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007070:Immunoglobulin A / Q000494:pharmacology; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical; D008895:Milk, Human / Q000276:immunology / Q000821:virology; D009092:Mucous Membrane / Q000276:immunology* / Q000821:virology*; D009500:Neutralization Tests; D011247:Pregnancy
chemical_list: D000911:Antibodies, Monoclonal; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160; D007070:Immunoglobulin A; C514797:gp160 protein, Human immunodeficiency virus 1; C034639:polymeric IgA