title: F(ab')2 fragment of a gp41 NHR-trimer-induced IgM monoclonal antibody neutralizes HIV-1 infection and blocks viral fusion by targeting the conserved gp41 pocket.
abstract: Using a recombinant protein N46FdFc that mimics the HIV-1 gp41 N-helix trimer to immunize mice, we identified the first IgM monoclonal antibody 18D3 that specifically bound to the conserved gp41 pocket. Its F(ab')2 fragment potently inhibited HIV-1 Env-mediated cell-cell fusion and neutralized infection by laboratory-adapted and primary HIV-1 isolates with different subtypes and tropism, including the T20-resistant variants. This F(ab')2 fragment can be used to develop a bispecific broad neutralizing monoclonal antibody or HIV-1 inactivator as a novel immunotherapeutic for treatment and prevention of HIV-1 infection.
authors.affiliation: Key Laboratory of Medical Molecular Virology of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai 200032, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Lu
authors.forename: Meili
authors.initials: M
authors.lastname: Wei
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Chen
authors.forename: Weiliang
authors.initials: W
authors.lastname: Xiong
authors.forename: Fei
authors.initials: F
authors.lastname: Yu
authors.forename: Zhi
authors.initials: Z
authors.lastname: Qi
authors.forename: Shibo
authors.initials: S
authors.lastname: Jiang
authors.forename: Chungen
authors.initials: C
authors.lastname: Pan
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D057134:Antibodies, Neutralizing / Q000276:immunology*; D015483:HIV Antibodies / Q000276:immunology*; D015700:HIV Envelope Protein gp41 / Q000276:immunology*; D015658:HIV Infections / Q000517:prevention & control / Q000628:therapy; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000276:immunology*; D007075:Immunoglobulin M / Q000276:immunology*; D051379:Mice
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D015483:HIV Antibodies; D015700:HIV Envelope Protein gp41; D007140:Immunoglobulin Fab Fragments; D007075:Immunoglobulin M; C514787:gp41 protein, Human immunodeficiency virus 1
keywords: HIV fusion inhibitor; HIV-1; Immunotherapeutics; Monoclonal antibody; gp41