Open AccessStructure basis of neutralization by a novel site II/IV antibody against respiratory syncytial virus fusion protein
Author(s) -
Qingqing Xie,
Zhao Wang,
Fengyun Ni,
Hong Chen,
Jianpeng Ma,
Nita Patel,
Huanzhang Lü,
Ye Liu,
Jing-Hui Tian,
David C. Flyer,
Michael J. Massare,
Larry Ellingsworth,
Gregory M. Glenn,
Gale Smith,
Qinghua Wang
Publication year - 2019
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0210749
Subject(s) - virology , neutralization , virus , paramyxoviridae , glycoprotein , monoclonal antibody , fusion protein , biology , antibody , antigen , microbiology and biotechnology , immunology , recombinant dna , viral disease , biochemistry , gene
Globally, human respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections in newborns, young children, and the elderly for which there is no vaccine. The RSV fusion (F) glycoprotein is a major target for vaccine development. Here, we describe a novel monoclonal antibody (designated as R4.C6) that recognizes both pre-fusion and post-fusion RSV F, and binds with nanomole affinity to a unique neutralizing site comprised of antigenic sites II and IV on the globular head. A 3.9 Å-resolution structure of RSV F-R4.C6 Fab complex was obtained by single particle cryo-electron microscopy and 3D reconstruction. The structure unraveled detailed interactions of R4.C6 with antigenic site II on one protomer and site IV on a neighboring protomer of post-fusion RSV F protein. These findings significantly further our understanding of the antigenic complexity of the F protein and provide new insights into RSV vaccine design.