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

Nature communications (2018-05-16)
Lars E Clark, Selma Mahmutovic, Donald D Raymond, Taleen Dilanyan, Takaaki Koma, John T Manning, Sundaresh Shankar, Silvana C Levis, Ana M Briggiler, Delia A Enria, Kai W Wucherpfennig, Slobodan Paessler, Jonathan Abraham
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Anti-Human IgG (Fab specific)−Peroxidase antibody produced in goat, affinity isolated antibody