Multifunctional human monoclonal antibody combination mediates protection against Rift Valley fever virus at low doses

被引：9

作者：

Chapman, Nathaniel S. ^{[1
,2
]}

Hulswit, Ruben J. G. ^{[3
]}

Westover, Jonna L. B. ^{[4
]}

Stass, Robert ^{[3
]}

Paesen, Guido C. ^{[3
]}

Binshtein, Elad ^{[2
]}

Reidy, Joseph X. ^{[2
]}

Engdahl, Taylor B. ^{[1
,2
]}

Handal, Laura S. ^{[2
]}

Flores, Alejandra ^{[1
]}

Gowen, Brian B. ^{[4
]}

Bowden, Thomas A. ^{[3
]}

Crowe, James E., Jr. ^{[1
,2
,5
]}

机构：

[1] Vanderbilt Univ, Dept Pathol Microbiol & Immunol, Med Ctr, Nashville, TN 37232 USA

[2] Vanderbilt Univ, Vanderbilt Vaccine Ctr, Med Ctr, Nashville, TN 37232 USA

[3] Univ Oxford, Wellcome Ctr Human Genet, Div Struct Biol, Roosevelt Dr, Oxford OX3 7BN, England

[4] Utah State Univ, Dept Anim Dairy & Vet Sci, Logan, UT 84322 USA

[5] Vanderbilt Univ, Dept Pediat, Med Ctr, Nashville, TN 37232 USA

来源：

NATURE COMMUNICATIONS | 2023年 / 14卷 / 01期

基金：

英国惠康基金; 英国医学研究理事会; 美国国家卫生研究院;

关键词：

RECEPTOR; NEUTRALIZATION; INFECTION; VACCINE; SYSTEM; IMMUNOGENICITY; ENCEPHALITIS; IMMUNIZATION; PREDICTION; DISEASE;

D O I：

10.1038/s41467-023-41171-3

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

The zoonotic Rift Valley fever virus (RVFV) can cause severe disease in humans and has pandemic potential, yet no approved vaccine or therapy exists. Here we describe a dual-mechanism human monoclonal antibody (mAb) combination against RVFV that is effective at minimal doses in a lethal mouse model of infection. We structurally analyze and characterize the binding mode of a prototypical potent Gn domain-A-binding antibody that blocks attachment and of an antibody that inhibits infection by abrogating the fusion process as previously determined. Surprisingly, the Gn domain-A antibody does not directly block RVFV Gn interaction with the host receptor low density lipoprotein receptor-related protein 1 (LRP1) as determined by a competitive assay. This study identifies a rationally designed combination of human mAbs deserving of future investigation for use in humans against RVFV infection. Using a two-pronged mechanistic approach, we demonstrate the potent efficacy of a rationally designed combination mAb therapeutic.

引用

页数：15

共 82 条

[1] PHENIX:: building new software for automated crystallographic structure determination [J].

Adams, PD ;

Grosse-Kunstleve, RW ;

Hung, LW ;

Ioerger, TR ;

McCoy, AJ ;

Moriarty, NW ;

Read, RJ ;

Sacchettini, JC ;

Sauter, NK ;

Terwilliger, TC .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2002, 58 :1948-1954

[2] A Protective Monoclonal Antibody Targets a Site of Vulnerability on the Surface of Rift Valley Fever Virus [J].

Allen, Elizabeth R. ;

Krumm, Stefanie A. ;

Raghwani, Jayna ;

Halldorsson, Steinar ;

Elliott, Angela ;

Graham, Victoria A. ;

Koudriakova, Elina ;

Harlos, Karl ;

Wright, Daniel ;

Warimwe, George M. ;

Brennan, Benjamin ;

Huiskonen, Juha T. ;

Dowall, Stuart D. ;

Elliott, Richard M. ;

Pybus, Oliver G. ;

Burton, Dennis R. ;

Hewson, Roger ;

Doores, Katie J. ;

Bowden, Thomas A. .

CELL REPORTS, 2018, 25 (13) :3750-+

[3] Crystal structure of the Fab region of a neutralizing antibody against granulocyte-macrophage colony-stimulating factor [J].

Angkawidjaja, Clement ;

Torashima, Takashi .

ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY COMMUNICATIONS, 2019, 75 :634-639

[4] Prediction of a Rift Valley fever outbreak [J].

Anyamba, Assaf ;

Chretien, Jean-Paul ;

Small, Jennifer ;

Tucker, Compton J. ;

Formenty, Pierre B. ;

Richardson, Jason H. ;

Britch, Seth C. ;

Schnabelf, David C. ;

Erickson, Ralph L. ;

Linthicum, Kenneth J. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (03) :955-959

[5] A time- and cost-efficient system for high-level protein production in mammalian cells [J].

Aricescu, A. Radu ;

Lu, Weixian ;

Jones, E. Yvonne .

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY, 2006, 62 :1243-1250

[6] Rift Valley fever: an uninvited zoonosis in the Arabian peninsula [J].

Balkhy, HH ;

Memish, ZA .

INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, 2003, 21 (02) :153-157

[7]

Baudin M, 2016, LANCET GLOB HEALTH, V4, pE864, DOI [10.1016/S2214-109X(16)30176-0, 10.1016/s2214-109x(16)30176-0]

[8] Complete genome ancalysis of 33 ecologically and biologically diverse rift valley fever virus strains reveals widespread virus movement and low genetic diversity due to recent common ancestry [J].

Bird, Brian H. ;

Khristova, Marina L. ;

Rollin, Pierre E. ;

Ksiazek, Thomas G. ;

Nichol, Stuart T. .

JOURNAL OF VIROLOGY, 2007, 81 (06) :2805-2816

[9] Closing the Rift: Discovery of a novel virus receptor [J].

Bopp, Nathen E. ;

Fernandez, Diana ;

Aguilar, Patricia V. .

CELL, 2021, 184 (20) :5084-5086

[10] Glycoprotein structural genomics: Solving the glycosylation problem [J].

Chang, Veronica T. ;

Crispin, Max ;

Aricescu, A. Radu ;

Harvey, David J. ;

Nettleship, Joanne E. ;

Fennelly, Janet A. ;

Yu, Chao ;

Boles, Keni S. ;

Evans, Edward J. ;

Stuart, David I. ;

Dwek, Raymond A. ;

Jones, E. Yvonne ;

Owens, Raymond J. ;

Davis, Simon J. .

STRUCTURE, 2007, 15 (03) :267-273

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