Human antibody recognition of antigenic site IV on Pneumovirus fusion proteins.

PLoS Pathogens
Jarrod J MousaJames E Crowe

Abstract

Respiratory syncytial virus (RSV) is a major human pathogen that infects the majority of children by two years of age. The RSV fusion (F) protein is a primary target of human antibodies, and it has several antigenic regions capable of inducing neutralizing antibodies. Antigenic site IV is preserved in both the pre-fusion and post-fusion conformations of RSV F. Antibodies to antigenic site IV have been described that bind and neutralize both RSV and human metapneumovirus (hMPV). To explore the diversity of binding modes at antigenic site IV, we generated a panel of four new human monoclonal antibodies (mAbs) and competition-binding suggested the mAbs bind at antigenic site IV. Mutagenesis experiments revealed that binding and neutralization of two mAbs (3M3 and 6F18) depended on arginine (R) residue R429. We discovered two R429-independent mAbs (17E10 and 2N6) at this site that neutralized an RSV R429A mutant strain, and one of these mAbs (17E10) neutralized both RSV and hMPV. To determine the mechanism of cross-reactivity, we performed competition-binding, recombinant protein mutagenesis, peptide binding, and electron microscopy experiments. It was determined that the human cross-reactive mAb 17E10 binds to RSV F with a binding...Continue Reading

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Citations

Mar 1, 2019·Vaccines·Emily PhungTracy J Ruckwardt
Feb 26, 2020·Pathogens·Daniela Ogonczyk MakowskaGuy Boivin
Dec 19, 2019·Frontiers in Immunology·Jiachen HuangJarrod J Mousa
Oct 10, 2020·PLoS Pathogens·Jiachen HuangJarrod J Mousa
Jan 6, 2021·Nature Chemical Biology·Che YangBruno E Correia
Mar 19, 2021·Expert Review of Vaccines·Brittani N BlunckPedro A Piedra
May 1, 2021·International Journal of Molecular Sciences·Alessandro RoccaMarcello Lanari

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Methods Mentioned

BETA
phage display
enzyme-linked immunosorbent assay
ELISA
flow cytometry
biosensors
biosensor
biolayer interferometry
electron microscopy
X-ray
density gradient centrifugation

Software Mentioned

cl2d
SerialEM
RELION
Prism
xmipp3

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