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Nat Commun. 2018 May 14;9(1):1884. doi: 10.1038/s41467-018-04271-z.

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

Author information

1
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, 02115, USA.
2
Laboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
3
Department of Pathology, University of Texas Medical Branch at Galveston, Galveston, TX, 77555, USA.
4
Instituto Nacional de Enfermedades Virales Humanas "Dr. Julio I. Maiztegui", Monteagudo 251 Pergamino, Buenos Aires, 2700, Argentina.
5
Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, 02115, USA.
6
Program in Immunology, Harvard Medical School, Boston, MA, 02115, USA.
7
Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA, 02115, USA. abraham@crystal.harvard.edu.
8
Laboratory of Molecular Medicine, Boston Children's Hospital, Harvard Medical School, Boston, MA, 02115, USA. abraham@crystal.harvard.edu.
9
Department of Medicine, Division of Infectious Diseases, Brigham and Women's Hospital, Boston, MA, 02115, USA. abraham@crystal.harvard.edu.

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.

PMID:
29760382
PMCID:
PMC5951886
DOI:
10.1038/s41467-018-04271-z
[Indexed for MEDLINE]
Free PMC Article

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