Distinct mechanisms of neutralization by antibodies targeting a conserved pneumovirus F epitope
- 1Division of Immunology and Respiratory Medicine, Department of Medicine Solna, Karolinska Institutet and Karolinska University Hospital, Stockholm, Sweden; Cent
Abstract
Pneumoviruses cause seasonal outbreaks leading to hospitalizations of vulnerable populations such as infants and the elderly. Cross-neutralizing antibodies targeting viral fusion have been isolated from infected individuals, but their elicitation and mechanisms of action remain understudied. Here, we describe two vaccine-elicited antibody classes, LOR24 and LOR69, that bind an overlapping epitope, and identify the somatic mutations that endow their breadth and potency, respectively. Cryo-electron microscopy structures of both antibodies bound to the HRSV fusion (F) protein show binding modes distinct from each other and from the previously described cross-neutralizing antibody MPE8, yet they all use similar motifs for binding. Complementary in vitro and electron microscopy experiments show that these antibodies either lock prefusion F as a trimer, arrest F in a monomeric or intermediate state, or promote the transition to the postfusion conformation. This work sheds light on mechanisms of pneumovirus neutralization and the elicitation of cross-neutralizing antibody responses.
Related
- Structural basis for broad orthopoxvirus neutralization by two antibodies targeting distinct L1R epitopes
- Dissociation kinetics and avidity gate SARS-CoV-2 neutralization by HR2 stem helix antibodies
- Phenuivirus glycoprotein Gc domain is a conserved target of cross-functional monoclonal antibodies
- Genetically restricted human antibodies recognize a conserved β-hairpin in postfusion influenza hemagglutinin
- Antibody 3CF5 neutralizes historical and emerging H5Nx influenza viruses by targeting a conserved non-receptor-binding hemagglutinin epitope
BibTeX
@misc{ols2026distinct,
title = {{Distinct mechanisms of neutralization by antibodies targeting a conserved pneumovirus F epitope}},
author = {S. Ols and R. Arcoverde Cerveira and A. J. Borst and E. Bermudez-Mendez and F. Gegenfurtner and E. Eray and C. Weidle and M. C. Miranda and Z. Peng and K. D. Carr and R. Skotheim and J. Kochmann and N. Brunette and K. Lenart and L. Hanke and G. B. Karlsson Hedestam and L. Perez and A. Antanasijevic and N. P. King and K. Lore},
howpublished = {bioRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.21.749132},
url = {https://www.biorxiv.org/content/10.64898/2026.09.21.749132v1},
note = {CC BY},
}
RIS
TY - UNPB
TI - Distinct mechanisms of neutralization by antibodies targeting a conserved pneumovirus F epitope
AU - S. Ols
AU - R. Arcoverde Cerveira
AU - A. J. Borst
AU - E. Bermudez-Mendez
AU - F. Gegenfurtner
AU - E. Eray
AU - C. Weidle
AU - M. C. Miranda
AU - Z. Peng
AU - K. D. Carr
AU - R. Skotheim
AU - J. Kochmann
AU - N. Brunette
AU - K. Lenart
AU - L. Hanke
AU - G. B. Karlsson Hedestam
AU - L. Perez
AU - A. Antanasijevic
AU - N. P. King
AU - K. Lore
PY - 2026
DA - 2026/09/21
PB - bioRxiv
DO - 10.64898/2026.09.21.749132
UR - https://www.biorxiv.org/content/10.64898/2026.09.21.749132v1
AB - Pneumoviruses cause seasonal outbreaks leading to hospitalizations of vulnerable populations such as infants and the elderly. Cross-neutralizing antibodies targeting viral fusion have been isolated from infected individuals, but their elicitation and mechanisms of action remain understudied. Here, we describe two vaccine-elicited antibody classes, LOR24 and LOR69, that bind an overlapping epitope, and identify the somatic mutations that endow their breadth and potency, respectively. Cryo-electron microscopy structures of both antibodies bound to the HRSV fusion (F) protein show binding modes distinct from each other and from the previously described cross-neutralizing antibody MPE8, yet they all use similar motifs for binding. Complementary in vitro and electron microscopy experiments show that these antibodies either lock prefusion F as a trimer, arrest F in a monomeric or intermediate state, or promote the transition to the postfusion conformation. This work sheds light on mechanisms of pneumovirus neutralization and the elicitation of cross-neutralizing antibody responses.
ER -