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

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.

Authors:
 [1];  [1];  [1];  [1];  [2];  [2];  [1];  [3];  [3];  [3];  [4];  [2]; ORCiD logo [5]
  1. Harvard Medical School, Boston, MA (United States)
  2. Univ. of Texas Medical Branch, Galveston, TX (United States)
  3. Inst. Nacional de Enfermedades Virales Humanas “Dr. Julio I. Maiztegui”, Buenos Aires (Argentina)
  4. Harvard Medical School, Boston, MA (United States); Dana-Farber Cancer Inst., Boston, MA (United States)
  5. Harvard Medical School, Boston, MA (United States); Brigham and Women's Hospital, Boston, MA (United States)
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
National Inst. of Health; NIAID
OSTI Identifier:
1440602
Grant/Contract Number:  
AI109740
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Nature Communications
Additional Journal Information:
Journal Volume: 9; Journal Issue: 1; Journal ID: ISSN 2041-1723
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
ENGLISH
Subject:
59 BASIC BIOLOGICAL SCIENCES; Antibodies; Arenaviruses; Immunological memory; Vaccines

Citation Formats

Clark, Lars E., 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 W., Paessler, Slobodan, and Abraham, Jonathan. Vaccine-elicited receptor-binding site antibodies neutralize two New World hemorrhagic fever arenaviruses. United States: N. p., 2018. Web. doi:10.1038/s41467-018-04271-z.
Clark, Lars E., 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 W., Paessler, Slobodan, & Abraham, Jonathan. Vaccine-elicited receptor-binding site antibodies neutralize two New World hemorrhagic fever arenaviruses. United States. doi:10.1038/s41467-018-04271-z.
Clark, Lars E., 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 W., Paessler, Slobodan, and Abraham, Jonathan. Mon . "Vaccine-elicited receptor-binding site antibodies neutralize two New World hemorrhagic fever arenaviruses". United States. doi:10.1038/s41467-018-04271-z. https://www.osti.gov/servlets/purl/1440602.
@article{osti_1440602,
title = {Vaccine-elicited receptor-binding site antibodies neutralize two New World hemorrhagic fever arenaviruses},
author = {Clark, Lars E. and Mahmutovic, Selma and Raymond, Donald D. and Dilanyan, Taleen and Koma, Takaaki and Manning, John T. and Shankar, Sundaresh and Levis, Silvana C. and Briggiler, Ana M. and Enria, Delia A. and Wucherpfennig, Kai W. and Paessler, Slobodan and Abraham, Jonathan},
abstractNote = {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.},
doi = {10.1038/s41467-018-04271-z},
journal = {Nature Communications},
issn = {2041-1723},
number = 1,
volume = 9,
place = {United States},
year = {2018},
month = {5}
}

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