Structure basis of neutralization by a novel site II/IV antibody against respiratory syncytial virus fusion protein.
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2019
2019
Historique:
received:
17
09
2018
accepted:
30
12
2018
entrez:
8
2
2019
pubmed:
8
2
2019
medline:
30
10
2019
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 30730999
doi: 10.1371/journal.pone.0210749
pii: PONE-D-18-25464
pmc: PMC6366758
doi:
Substances chimiques
Antibodies, Neutralizing
0
Antibodies, Viral
0
Immunoglobulin Fab Fragments
0
Viral Fusion Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0210749Subventions
Organisme : NIGMS NIH HHS
ID : R01 GM116280
Pays : United States
Organisme : NIGMS NIH HHS
ID : R01 GM127628
Pays : United States
Déclaration de conflit d'intérêts
The authors have read the journal's policy and have the following conflicts: NP, HL, YL, JHT, DF, MJM, LE, GG, and GS are current or past employees of Novavax, Inc., and own or hold stock options. There are no patents, products in development, or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials.
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