(Nature Publishing Group UK, 2018) Clark, Lars; Mahmutovic, Selma; Raymond, Donald D.; Dilanyan, Taleen; Koma, Takaaki; Manning, John T.; Shankar, Sundaresh; Levis, Silvana C.; Briggiler, Ana M.; Enria, Delia A.; Wucherpfennig, Kai; Paessler, Slobodan; Abraham, Jonathan
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.
