A monoclonal antibody targeting the Nipah virus fusion glycoprotein apex imparts protection from disease

Victoria A. Avanzato; Trenton Bushmaker; Kasopefoluwa Y. Oguntuyo; Claude Kwe Yinda; Helen M.E. Duyvesteyn; Robert Stass; Kimberly Meade-White; Rebecca Rosenke; Tina Thomas; Neeltje van Doremalen; Greg Saturday; Katie J. Doores; Benhur Lee; Thomas A. Bowden; Vincent J. Munster

doi:10.1128/jvi.00638-24

A monoclonal antibody targeting the Nipah virus fusion glycoprotein apex imparts protection from disease

Victoria A. Avanzato, Trenton Bushmaker, Kasopefoluwa Y. Oguntuyo, Claude Kwe Yinda, Helen M.E. Duyvesteyn, Robert Stass, Kimberly Meade-White, Rebecca Rosenke, Tina Thomas, Neeltje van Doremalen, Greg Saturday, Katie J. Doores, Benhur Lee, Thomas A. Bowden, Vincent J. Munster^*

^*Corresponding author for this work

Infectious Diseases

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

Abstract

Nipah virus (NiV) is a highly pathogenic paramyxovirus capable of causing severe respiratory and neurologic disease in humans. Currently, there are no licensed vaccines or therapeutics against NiV, underscoring the urgent need for the development of countermeasures. The NiV surface-displayed glycoproteins, NiV-G and NiV-F, mediate host cell attachment and fusion, respectively, and are heavily targeted by host antibodies. Here, we describe a vaccination-derived neutralizing monoclonal antibody, mAb92, that targets NiV-F. Structural characterization of the Fab region bound to NiV-F (NiV-F-Fab92) by cryo-electron microscopy analysis reveals an epitope in the DIII domain at the membrane distal apex of NiV-F, an established site of vulnerability on the NiV surface. Further, prophylactic treatment of hamsters with mAb92 offeredcomplete protection from NiV disease, demonstrating beneficialactivity of mAb92 in vivo. This work provides support for targeting NiV-F in the development of vaccines and therapeutics against NiV.

Original language	English
Article number	e00638-24
Journal	Journal of Virology
Volume	98
Issue number	10
DOIs	https://doi.org/10.1128/jvi.00638-24
Publication status	Published - Oct 2024

Keywords

fusion glycoprotein
henipavirus
monoclonal antibodies
neutralizing antibodies
Nipah virus

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1128/jvi.00638-24

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Avanzato, V. A., Bushmaker, T., Oguntuyo, K. Y., Yinda, C. K., Duyvesteyn, H. M. E., Stass, R., Meade-White, K., Rosenke, R., Thomas, T., van Doremalen, N., Saturday, G., Doores, K. J., Lee, B., Bowden, T. A., & Munster, V. J. (2024). A monoclonal antibody targeting the Nipah virus fusion glycoprotein apex imparts protection from disease. Journal of Virology, 98(10), Article e00638-24. https://doi.org/10.1128/jvi.00638-24

@article{1756c1f5543845f9a57a7db5537e20cc,

title = "A monoclonal antibody targeting the Nipah virus fusion glycoprotein apex imparts protection from disease",

abstract = "Nipah virus (NiV) is a highly pathogenic paramyxovirus capable of causing severe respiratory and neurologic disease in humans. Currently, there are no licensed vaccines or therapeutics against NiV, underscoring the urgent need for the development of countermeasures. The NiV surface-displayed glycoproteins, NiV-G and NiV-F, mediate host cell attachment and fusion, respectively, and are heavily targeted by host antibodies. Here, we describe a vaccination-derived neutralizing monoclonal antibody, mAb92, that targets NiV-F. Structural characterization of the Fab region bound to NiV-F (NiV-F-Fab92) by cryo-electron microscopy analysis reveals an epitope in the DIII domain at the membrane distal apex of NiV-F, an established site of vulnerability on the NiV surface. Further, prophylactic treatment of hamsters with mAb92 offeredcomplete protection from NiV disease, demonstrating beneficialactivity of mAb92 in vivo. This work provides support for targeting NiV-F in the development of vaccines and therapeutics against NiV.",

keywords = "fusion glycoprotein, henipavirus, monoclonal antibodies, neutralizing antibodies, Nipah virus",

author = "Avanzato, {Victoria A.} and Trenton Bushmaker and Oguntuyo, {Kasopefoluwa Y.} and Yinda, {Claude Kwe} and Duyvesteyn, {Helen M.E.} and Robert Stass and Kimberly Meade-White and Rebecca Rosenke and Tina Thomas and {van Doremalen}, Neeltje and Greg Saturday and Doores, {Katie J.} and Benhur Lee and Bowden, {Thomas A.} and Munster, {Vincent J.}",

note = "Publisher Copyright: {\textcopyright} 2024 American Society for Microbiology.",

year = "2024",

month = oct,

doi = "10.1128/jvi.00638-24",

language = "English",

volume = "98",

journal = "Journal of Virology",

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publisher = "American Society for Microbiology",

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Avanzato, VA, Bushmaker, T, Oguntuyo, KY, Yinda, CK, Duyvesteyn, HME, Stass, R, Meade-White, K, Rosenke, R, Thomas, T, van Doremalen, N, Saturday, G, Doores, KJ, Lee, B, Bowden, TA & Munster, VJ 2024, 'A monoclonal antibody targeting the Nipah virus fusion glycoprotein apex imparts protection from disease', Journal of Virology, vol. 98, no. 10, e00638-24. https://doi.org/10.1128/jvi.00638-24

TY - JOUR

T1 - A monoclonal antibody targeting the Nipah virus fusion glycoprotein apex imparts protection from disease

AU - Avanzato, Victoria A.

AU - Bushmaker, Trenton

AU - Oguntuyo, Kasopefoluwa Y.

AU - Yinda, Claude Kwe

AU - Duyvesteyn, Helen M.E.

AU - Stass, Robert

AU - Meade-White, Kimberly

AU - Rosenke, Rebecca

AU - Thomas, Tina

AU - van Doremalen, Neeltje

AU - Saturday, Greg

AU - Doores, Katie J.

AU - Lee, Benhur

AU - Bowden, Thomas A.

AU - Munster, Vincent J.

PY - 2024/10

Y1 - 2024/10

N2 - Nipah virus (NiV) is a highly pathogenic paramyxovirus capable of causing severe respiratory and neurologic disease in humans. Currently, there are no licensed vaccines or therapeutics against NiV, underscoring the urgent need for the development of countermeasures. The NiV surface-displayed glycoproteins, NiV-G and NiV-F, mediate host cell attachment and fusion, respectively, and are heavily targeted by host antibodies. Here, we describe a vaccination-derived neutralizing monoclonal antibody, mAb92, that targets NiV-F. Structural characterization of the Fab region bound to NiV-F (NiV-F-Fab92) by cryo-electron microscopy analysis reveals an epitope in the DIII domain at the membrane distal apex of NiV-F, an established site of vulnerability on the NiV surface. Further, prophylactic treatment of hamsters with mAb92 offeredcomplete protection from NiV disease, demonstrating beneficialactivity of mAb92 in vivo. This work provides support for targeting NiV-F in the development of vaccines and therapeutics against NiV.

AB - Nipah virus (NiV) is a highly pathogenic paramyxovirus capable of causing severe respiratory and neurologic disease in humans. Currently, there are no licensed vaccines or therapeutics against NiV, underscoring the urgent need for the development of countermeasures. The NiV surface-displayed glycoproteins, NiV-G and NiV-F, mediate host cell attachment and fusion, respectively, and are heavily targeted by host antibodies. Here, we describe a vaccination-derived neutralizing monoclonal antibody, mAb92, that targets NiV-F. Structural characterization of the Fab region bound to NiV-F (NiV-F-Fab92) by cryo-electron microscopy analysis reveals an epitope in the DIII domain at the membrane distal apex of NiV-F, an established site of vulnerability on the NiV surface. Further, prophylactic treatment of hamsters with mAb92 offeredcomplete protection from NiV disease, demonstrating beneficialactivity of mAb92 in vivo. This work provides support for targeting NiV-F in the development of vaccines and therapeutics against NiV.

KW - fusion glycoprotein

KW - henipavirus

KW - monoclonal antibodies

KW - neutralizing antibodies

KW - Nipah virus

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U2 - 10.1128/jvi.00638-24

DO - 10.1128/jvi.00638-24

M3 - Article

C2 - 39240113

AN - SCOPUS:85207597551

SN - 0022-538X

VL - 98

JO - Journal of Virology

JF - Journal of Virology

IS - 10

M1 - e00638-24

ER -

A monoclonal antibody targeting the Nipah virus fusion glycoprotein apex imparts protection from disease

Abstract

Keywords

UN SDGs

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