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ID 112467
Clark, Lars E. Harvard Medical School
Mahmutovic, Selma Harvard Medical School
Raymond, Donald D. Harvard Medical School
Dilanyan, Taleen Harvard Medical School
Manning, John T. University of Texas Medical Branch at Galveston
Shankar, Sundaresh Harvard Medical School
Levis, Silvana C. Instituto Nacional de Enfermedades Virales Humanas
Briggiler, Ana M. Instituto Nacional de Enfermedades Virales Humanas
Enria, Delia A. Instituto Nacional de Enfermedades Virales Humanas
Wucherpfennig, Kai W. Harvard Medical School|Dana-Farber Cancer Institute
Paessler, Slobodan University of Texas Medical Branch at Galveston
Abraham, Jonathan Harvard Medical School|Brigham and Women’s Hospital
Content Type
Journal Article
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.
Journal Title
Nature Communications
Springer Nature
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Published Date
Supplementary Information : ncomms_9_1884_s1.pdf
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Medical Sciences