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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
Institution:1. Key Laboratory of Medical Molecular Virology of Education and Health, Shanghai Medical College and Institute of Medical Microbiology, Fudan University, Shanghai 200032, China;2. The Institute of Human Virology, Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-Sen University, Guangzhou 510080, China;3. Lindsley F. Kimball Research Institute, New York Blood Center, New York, NY 10065, USA;1. Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Building 224, DK-2800 Kgs. Lyngby, Denmark;2. Department of Microbiology and Risk Assessment, The National Food Institute, Technical University of Denmark, Mørkhøj Bygade 19, DK-2860 Søborg, Denmark;3. Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, Copenhagen University, Ridebanevej 9, DK-1871 Frederiksberg C, Denmark;1. Department of Pathology and Laboratory Medicine, Medical Sciences I, Room D440, University of California, Irvine, Irvine, CA 92697-4800, USA;2. Section of Infectious Diseases, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA;1. Departamento de Biotecnología y Bioingeniería, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Av. IPN # 2508, Col. San Pedro Zacatenco, Delg. Gustavo A. Madero, CP 07360 México, DF, Mexico;2. Departamento de Infectómica y Patogénesis Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional (CINVESTAV-IPN), Av. IPN # 2508, Col. San Pedro Zacatenco, Delg. Gustavo A. Madero, CP 07360 México, DF, Mexico;3. Laboratório de Ultraestrutura Celular, Universidade Santa Úrsula, Rua Jornalista Orlando Dantas 36, Botafogo, CEP 22231-010 Rio de Janeiro, Brazil;1. International Centre for Diarrhoeal Disease Research, Bangladesh, 1212 Dhaka, Bangladesh;2. Departamento de Salud Pública, Facultad de Medicina, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico;3. Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77 Stockholm, Sweden;4. Institute of Biology and Biomedical Center, University of Iceland, 101 Reykjavik, Iceland;1. Núcleo de Neurociências, Departamento de Fisiologia e Biofísica, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG 31270-901, Brazil;2. Departamento de Cirurgia, Faculdade de Medicina, Universidade Federal de Minas Gerais, Av. Professor Alfredo Balena, 190, Santa Efigênia, Belo Horizonte, MG 30130-100, Brazil;3. Departamento de Patologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Av. Antônio Carlos, 6627, Pampulha, Belo Horizonte, MG 31270-901, Brazil
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.
Keywords:HIV-1  gp41  Monoclonal antibody  HIV fusion inhibitor  Immunotherapeutics
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