The respiratory syncytial virus (RSV) prefusion F-protein functional antibody repertoire in adult healthy donors

被引：23

作者：

Andreano, Emanuele ^{[1
,2
,5
]}

Paciello, Ida ^{[2
,5
]}

Bardelli, Monia ^{[2
]}

Tavarini, Simona ^{[2
]}

Sammicheli, Chiara ^{[2
]}

Frigimelica, Elisabetta ^{[2
]}

Guidotti, Silvia ^{[2
]}

Torricelli, Giulia ^{[2
]}

Biancucci, Marco ^{[3
]}

D'Oro, Ugo ^{[2
]}

Chandramouli, Sumana ^{[3
,6
]}

Bottomley, Matthew J. ^{[3
]}

Rappuoli, Rino ^{[2
,4
,5
]}

Finco, Oretta ^{[2
]}

Buricchi, Francesca ^{[2
]}

机构：

[1] Univ Siena, Dept Life Sci, Siena, Italy

[2] GSK Vaccines, Siena, Italy

[3] GSK Vaccines, Rockville, MD USA

[4] Imperial Coll, Fac Med, London, England

[5] Fdn Toscana Life Sci, Monoclonal Antibody Discovery MAD Lab, Siena, Italy

[6] Moderna Therapeut Inc, Cambridge, MA USA

来源：

EMBO MOLECULAR MEDICINE | 2021年 / 13卷 / 06期

关键词：

functional antibody repertoire; human monoclonal antibodies; RSV; vaccine development; FUSION GLYCOPROTEIN; STRUCTURAL BASIS; VACCINE; INFECTION; NEUTRALIZATION; EPITOPE;

D O I：

10.15252/emmm.202114035

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Respiratory syncytial virus (RSV) is the leading cause of death from lower respiratory tract infection in infants and children, and is responsible for considerable morbidity and mortality in older adults. Vaccines for pregnant women and elderly which are in phase III clinical studies target people with pre-existing natural immunity against RSV. To investigate the background immunity which will be impacted by vaccination, we single cell-sorted human memory B cells and dissected functional and genetic features of neutralizing antibodies (nAbs) induced by natural infection. Most nAbs recognized both the prefusion and postfusion conformations of the RSV F-protein (cross-binders) while a smaller fraction bound exclusively to the prefusion conformation. Cross-binder nAbs used a wide array of gene rearrangements, while preF-binder nAbs derived mostly from the expansion of B-cell clonotypes from the IGHV1 germline. This latter class of nAbs recognizes an epitope located between Site o, Site II, and Site V on the F-protein, identifying an important site of pathogen vulnerability.

引用

页数：15

共 54 条

[1]

AAP, 2014, PEDIATRICS, V134, P638

[2] Structural Determination of the Broadly Reactive Anti-IGHV1-69 Anti-idiotypic Antibody G6 and Its Idiotope [J].

Avnir, Yuval ;

Prachanronarong, Kristina L. ;

Zhang, Zhen ;

Hou, Shurong ;

Peterson, Eric C. ;

Sui, Jianhua ;

Zayed, Hatem ;

Kurella, Vinodh B. ;

McGuire, Andrew T. ;

Stamatatos, Leonidas ;

Hilbert, Brendan J. ;

Bohn, Markus-Frederik ;

Kowalik, Timothy F. ;

Jensen, Jeffrey D. ;

Finberg, Robert W. ;

Wang, Jennifer P. ;

Goodall, Margaret ;

Jefferis, Roy ;

Zhu, Quan ;

Yilmaz, Nese Kurt ;

Schiffer, Celia A. ;

Marasco, Wayne A. .

CELL REPORTS, 2017, 21 (11) :3243-3255

[3] IGHV1-69 polymorphism modulates anti-influenza antibody repertoires, correlates with IGHV utilization shifts and varies by ethnicity [J].

Avnir, Yuval ;

Watson, Corey T. ;

Glanville, Jacob ;

Peterson, Eric C. ;

Tallarico, Aimee S. ;

Bennett, Andrew S. ;

Qin, Kun ;

Fu, Ying ;

Huang, Chiung-Yu ;

Beigel, John H. ;

Breden, Felix ;

Zhu, Quan ;

Marasco, Wayne A. .

SCIENTIFIC REPORTS, 2016, 6

[4] Neuraminidase treatment of respiratory syncytial virus-infected cells or virions, but not target cells, enhances cell-cell fusion and infection [J].

Barretto, N ;

Hallak, LK ;

Peeples, ME .

VIROLOGY, 2003, 313 (01) :33-43

[5] Maturation Pathway from Germline to Broad HIV-1 Neutralizer of a CD4-Mimic Antibody [J].

Bonsignori, Mattia ;

Zhou, Tongqing ;

Sheng, Zizhang ;

Chen, Lei ;

Gao, Feng ;

Joyce, M. Gordon ;

Ozorowski, Gabriel ;

Chuang, Gwo-Yu ;

Schramm, Chaim A. ;

Wiehe, Kevin ;

Alam, S. Munir ;

Bradley, Todd ;

Gladden, Morgan A. ;

Hwang, Kwan-Ki ;

Iyengar, Sheelah ;

Kumar, Amit ;

Lu, Xiaozhi ;

Luo, Kan ;

Mangiapani, Michael C. ;

Parks, Robert J. ;

Song, Hongshuo ;

Acharya, Priyamvada ;

Bailer, Robert T. ;

Cao, Allen ;

Druz, Aliaksandr ;

Georgiev, Ivelin S. ;

Kwon, Young D. ;

Louder, Mark K. ;

Zhang, Baoshan ;

Zheng, Anqi ;

Hill, Brenna J. ;

Kong, Rui ;

Soto, Cinque ;

Mullikin, James C. ;

Douek, Daniel C. ;

Montefiori, David C. ;

Moody, Michael A. ;

Shaw, George M. ;

Hahn, Beatrice H. ;

Kelsoe, Garnett ;

Hraber, Peter T. ;

Korber, Bette T. ;

Boyd, Scott D. ;

Fire, Andrew Z. ;

Kepler, Thomas B. ;

Shapiro, Lawrence ;

Ward, Andrew B. ;

Mascola, John R. ;

Liao, Hua-Xin ;

Kwong, Peter D. .

CELL, 2016, 165 (02) :449-463

[6] High-throughput antibody sequencing reveals genetic evidence of global regulation of the naive and memory repertoires that extends across individuals [J].

Briney, B. S. ;

Willis, J. R. ;

McKinney, B. A. ;

Crowe, J. E., Jr. .

GENES AND IMMUNITY, 2012, 13 (06) :469-473

[7] Electron microscopy of the human respiratory syncytial virus fusion protein and complexes that it forms with monoclonal antibodies [J].

Calder, LJ ;

González-Reyes, L ;

García-Barreno, B ;

Wharton, SA ;

Skehel, LJ ;

Wiley, DC ;

Melero, JA .

VIROLOGY, 2000, 271 (01) :122-131

[8] Viral and host factors in human respiratory syncytial virus pathogenesis [J].

Collins, Peter L. ;

Graham, Barney S. .

JOURNAL OF VIROLOGY, 2008, 82 (05) :2040-2055

[9]

Collins PL., 2007, FIELDS VIROLOGY, V2, P1601

[10] Cross-neutralization of four paramyxoviruses by a human monoclonal antibody [J].

Corti, Davide ;

Bianchi, Siro ;

Vanzetta, Fabrizia ;

Minola, Andrea ;

Perez, Laurent ;

Agatic, Gloria ;

Guarino, Barbara ;

Silacci, Chiara ;

Marcandalli, Jessica ;

Marsland, Benjamin J. ;

Piralla, Antonio ;

Percivalle, Elena ;

Sallusto, Federica ;

Baldanti, Fausto ;

Lanzavecchia, Antonio .

NATURE, 2013, 501 (7467) :439-+

← 1 2 3 4 5 6 →