Vaccine-elicited receptor-binding site antibodies neutralize two New World hemorrhagic fever arenaviruses

• Autores: Clark, Lars E; Mahmutovic, Selma; Raymond, Donald D; Dilanyan, Taleen; Koma, Takaaki; Manning, John T; Shankar, Sundaresh; Levis, Silvana; Briggiler, Ana M.; Enria, Delia; Wucherpfennig, Kai W; Paessler, Slobodan; Abraham, Jonathan
• Año de publicación: 2018
• Idioma: inglés
• Tipo de recurso: artículo
• Fuente: Nature Communications 2018 ;9(1):1884.
• Materia: Arenavirus; Fiebre Hemorrágica Americana
• Institución: Administración Nacional de Laboratorios e Institutos de Salud "Dr. Carlos G. Malbrán"

Fil: Clark, Lars E. Department of Microbiology and Immunobiology, Harvard Medical School, Boston; Estados Unidos.
Fil: Mahmutovic, Selma. Laboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston; Estados Unidos.
Fil: Raymond, Donald D. Laboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston; Estados Unidos.
Fil: Dilanyan, Taleen. Department of Microbiology and Immunobiology, Harvard Medical School, Boston; Estados Unidos.
Fil: Koma, Takaaki. Department of Pathology, University of Texas Medical Branch at Galveston, Galveston; Estados Unidos.
Fil: Manning, John T. Department of Pathology, University of Texas Medical Branch at Galveston, Galveston; Estados Unidos.
Fil: Shankar, Sundaresh. Department of Microbiology and Immunobiology, Harvard Medical School, Boston; Estados Unidos.
Fil: Levis, Silvana C. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas; Argentina.
Fil: Briggiler, Ana M. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas; Argentina.
Fil: Enria, Delia A. ANLIS Dr.C.G.Malbrán. Instituto Nacional de Enfermedades Virales Humanas; Argentina.
Fil: Wucherpfennig, Kai W. Laboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston; Estados Unidos.
Fil: Paessler, Slobodan. Department of Pathology, University of Texas Medical Branch at Galveston, Galveston; Estados Unidos.
Fil: Abraham, Jonathan. Department of Microbiology and Immunobiology, Harvard Medical School, Boston; Estados Unidos.
While five arenaviruses cause human hemorrhagic fevers in the Western Hemisphere, only Junin virus (JUNV) has a vaccine. The GP1 subunit of their envelope glycoprotein binds transferrin receptor 1 (TfR1) using a surface that substantially varies in sequence among the viruses. As such, receptor-mimicking antibodies described to date are type-specific and lack the usual breadth associated with this mode of neutralization. Here we isolate, from the blood of a recipient of the live attenuated JUNV vaccine, two antibodies that cross-neutralize Machupo virus with varying efficiency. Structures of GP1-Fab complexes explain the basis for efficient cross-neutralization, which involves avoiding receptor mimicry and targeting a conserved epitope within the receptor-binding site (RBS). The viral RBS, despite its extensive sequence diversity, is therefore a target for cross-reactive antibodies with activity against New World arenaviruses of public health concern.