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

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

doi:10.1038/s41467-018-04271-z

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

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

Pathology

Research output: Contribution to journal › Article › peer-review

34 Scopus citations

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.

Original language	English (US)
Article number	1884
Journal	Nature communications
Volume	9
Issue number	1
DOIs	https://doi.org/10.1038/s41467-018-04271-z
State	Published - Dec 1 2018

ASJC Scopus subject areas

General Chemistry
General Biochemistry, Genetics and Molecular Biology
General Physics and Astronomy

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Clark, L. E., Mahmutovic, S., Raymond, D. D., Dilanyan, T., Koma, T., Manning, J. T., Shankar, S., Levis, S. C., Briggiler, A. M., Enria, D. A., Wucherpfennig, K. W., Paessler, S., & Abraham, J. (2018). Vaccine-elicited receptor-binding site antibodies neutralize two New World hemorrhagic fever arenaviruses. Nature communications, 9(1), Article 1884. https://doi.org/10.1038/s41467-018-04271-z

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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.",

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AU - Manning, John T.

AU - Shankar, Sundaresh

AU - Levis, Silvana C.

AU - Briggiler, Ana M.

AU - Enria, Delia A.

AU - Wucherpfennig, Kai W.

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AU - Abraham, Jonathan

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

Abstract

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