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 offered complete protection from NiV disease, demonstrating beneficial activity of mAb92 in vivo. This work provides support for targeting NiV-F in the development of vaccines and therapeutics against NiV..
| Medienart: |
|
|---|
Preprint| Erscheinungsjahr: |
2022 |
|---|---|
| Erschienen: |
2022 |
| Enthalten in: |
bioRxiv.org - (2022) vom: 28. Sept. Zur Gesamtaufnahme - year:2022 |
|---|
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Avanzato, Victoria A. [VerfasserIn] |
|---|
| Links: |
Volltext [kostenfrei] |
|---|
| Themen: |
|---|
| doi: |
10.1101/2022.09.26.507980 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
XBI037415808 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | XBI037415808 | ||
| 003 | DE-627 | ||
| 005 | 20230429082417.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 220929s2022 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1101/2022.09.26.507980 |2 doi | |
| 035 | |a (DE-627)XBI037415808 | ||
| 035 | |a (biorXiv)10.1101/2022.09.26.507980 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Avanzato, Victoria A. |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a A monoclonal antibody targeting the Nipah virus fusion glycoprotein apex imparts protection from disease |
| 264 | 1 | |c 2022 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a 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 offered complete protection from NiV disease, demonstrating beneficial activity of mAb92 in vivo. This work provides support for targeting NiV-F in the development of vaccines and therapeutics against NiV. | ||
| 650 | 4 | |a Biology |7 (dpeaa)DE-84 | |
| 650 | 4 | |a 570 |7 (dpeaa)DE-84 | |
| 700 | 1 | |a Bushmaker, Trenton |e verfasserin |4 aut | |
| 700 | 1 | |a Oguntuyo, Kasopefoluwa Y. |e verfasserin |4 aut | |
| 700 | 1 | |a Yinda, Kwe Claude |e verfasserin |4 aut | |
| 700 | 1 | |a Duyvesteyn, Helen M. E. |e verfasserin |4 aut | |
| 700 | 1 | |a Stass, Robert |e verfasserin |4 aut | |
| 700 | 1 | |a Meade-White, Kimberly |e verfasserin |4 aut | |
| 700 | 1 | |a Rosenke, Rebecca |e verfasserin |4 aut | |
| 700 | 1 | |a Thomas, Tina |e verfasserin |4 aut | |
| 700 | 1 | |a Saturday, Greg |e verfasserin |4 aut | |
| 700 | 1 | |a Doores, Katie J. |e verfasserin |4 aut | |
| 700 | 1 | |a Lee, Benhur |e verfasserin |4 aut | |
| 700 | 1 | |a Bowden, Thomas A. |e verfasserin |4 aut | |
| 700 | 1 | |a Munster, Vincent J. |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t bioRxiv.org |g (2022) vom: 28. Sept. |
| 773 | 1 | 8 | |g year:2022 |g day:28 |g month:09 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1101/2022.09.26.507980 |z kostenfrei |3 Volltext |
| 912 | |a GBV_XBI | ||
| 912 | |a SSG-OLC-PHA | ||
| 951 | |a AR | ||
| 952 | |j 2022 |b 28 |c 09 | ||