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

Publication Type:

Journal Article

Source:

Nat Commun, Volume 9, Issue 1, p.1884 (2018)

Abstract:

<p>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&nbsp;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.</p>

PDB: 
5W1G, 5W1M, 5W1K
Detector: 
Q315
PILATUS
Beamline: 
24-ID-C
24-ID-E