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

Nature Communications
Lars ClarkJonathan 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.

References

Jul 1, 1990·Journal of Virological Methods·J G Barrera OroJ I Maiztegui
Feb 18, 1998·The Journal of Infectious Diseases·J I MaizteguiC J Peters
Jan 15, 2003·Journal of Medical Virology·María del Carmen SaavedraAna María Ambrosio
Mar 5, 2003·Antiviral Research·Rémi N Charrel, Xavier de Lamballerie
Apr 16, 2005·Science·Kartik ChandranJames M Cunningham
Sep 27, 2006·Acta Crystallographica. Section D, Biological Crystallography·A Radu AricescuE Yvonne Jones
Dec 21, 2007·Acta Crystallographica. Section D, Biological Crystallography·Fei LongGarib N Murshudov
Feb 13, 2008·Proceedings of the National Academy of Sciences of the United States of America·Sheli R RadoshitzkyMichael Farzan
Jan 1, 1997·Methods in Enzymology·K Y ZhangP Main
Aug 1, 2007·Journal of Applied Crystallography·Airlie J McCoyRandy J Read
Jun 6, 2009·Journal of Virology·Thomas A BowdenDavid I Stuart
Jan 9, 2010·Acta Crystallographica. Section D, Biological Crystallography·Vincent B ChenDavid C Richardson
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Wolfgang Kabsch
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Mar 9, 2010·Nature Structural & Molecular Biology·Jonathan AbrahamStephen C Harrison
Apr 13, 2010·Acta Crystallographica. Section D, Biological Crystallography·P EmsleyK Cowtan
Apr 5, 2011·Acta Crystallographica. Section D, Biological Crystallography·Martyn D WinnKeith S Wilson
May 23, 2012·Proceedings of the National Academy of Sciences of the United States of America·Gui-Mei LiRafi Ahmed
May 26, 2012·Science·P Andrew Karplus, Kay Diederichs
Oct 3, 2012·PLoS Pathogens·Gilda GrardEric M Leroy
Nov 6, 2012·Annual Review of Pathology·Slobodan Paessler, David H Walker
Nov 24, 2012·Proceedings of the National Academy of Sciences of the United States of America·Aaron G SchmidtStephen C Harrison
Dec 4, 2012·Viruses·Dominique J BurriAntonella Pasquato
Feb 12, 2013·Nature Structural & Molecular Biology·Rui XuIan A Wilson
May 15, 2013·Nucleic Acids Research·Jian YeJames M Ostell
May 23, 2013·PLoS Pathogens·Jonathan D Cook, Jeffrey E Lee
Jun 1, 2013·PLoS Biology·Ann DemoginesSara L Sawyer
Sep 17, 2013·ELife·Andrew MorinPiotr Sliz
Apr 23, 2014·Nucleic Acids Research·Xavier Robert, Patrice Gouet
Jun 13, 2014·Journal of Virology·Min ZongHyeryun Choe
Aug 30, 2014·Nature·Xiangguo QiuGary P Kobinger
Nov 19, 2014·Proceedings of the National Academy of Sciences of the United States of America·Charles D MurinErica Ollmann Saphire
Feb 28, 2015·Cell·Andrew I FlyakJames E Crowe
May 12, 2015·Cell·Aaron G SchmidtStephen C Harrison
May 15, 2015·Journal of Virology·Hadas Cohen-DvashiRon Diskin

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Citations

Jan 5, 2020·Nature Communications·Hadas Cohen-DvashiRon Diskin
Feb 18, 2020·Virus Evolution·Weng M NgThomas A Bowden
Dec 1, 2020·PLoS Pathogens·Feifei ZhangMark E J Woolhouse
Dec 29, 2020·PLoS Neglected Tropical Diseases·Hector MorenoStefan Kunz
Jan 9, 2021·Science·Naphak ModhiranDaniel Watterson
Mar 2, 2021·PLoS Pathogens·Takaaki KomaSlobodan Paessler
Feb 22, 2021·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·Maria G FrankUNKNOWN members of the Medical Countermeasures Working Group of the National Emerging Special Pathogens Training and Education Cente
Apr 22, 2021·Proceedings of the National Academy of Sciences of the United States of America·Danny D SahtoeDavid Baker
Jan 23, 2019·Antiviral Research·Anne LeskeAllison Groseth

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Datasets Mentioned

BETA
D10072
ACY70854.1
MH151333
MH151334
MH151335
MH151336
MH151337
MH151338

Methods Mentioned

BETA
X-ray
ELISA
FACS
surface plasmon resonance
ELISAs
glycosylation
PCR
flow cytometry
size-exclusion chromatography
electrophoresis

Software Mentioned

ESPrit3
MolProbity
SBGrid
COOT
BiaEvaluation
PHASER
XSCALE
PHENIX
PyMol Molecular Graphics System
CCP4

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