Plant virus-derived nanoparticles decorated with genetically encoded SARS-CoV-2 nanobodies display enhanced neutralizing activity
© 2023 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd..
Viral nanoparticles (VNPs) are a new class of virus-based formulations that can be used as building blocks to implement a variety of functions of potential interest in biotechnology and nanomedicine. Viral coat proteins (CP) that exhibit self-assembly properties are particularly appropriate for displaying antigens and antibodies, by generating multivalent VNPs with therapeutic and diagnostic potential. Here, we developed genetically encoded multivalent VNPs derived from two filamentous plant viruses, potato virus X (PVX) and tobacco etch virus (TEV), which were efficiently and inexpensively produced in the biofactory Nicotiana benthamiana plant. PVX and TEV-derived VNPs were decorated with two different nanobodies recognizing two different regions of the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein. The addition of different picornavirus 2A ribosomal skipping peptides between the nanobody and the CP allowed for modulating the degree of VNP decoration. Nanobody-decorated VNPs purified from N. benthamiana tissues successfully recognized the RBD antigen in enzyme-linked immunosorbent assays and showed efficient neutralization activity against pseudoviruses carrying the Spike protein. Interestingly, multivalent PVX and TEV-derived VNPs exhibited a neutralizing activity approximately one order of magnitude higher than the corresponding nanobody in a dimeric format. These properties, combined with the ability to produce VNP cocktails in the same N. benthamiana plant based on synergistic infection of the parent PVX and TEV, make these green nanomaterials an attractive alternative to standard antibodies for multiple applications in diagnosis and therapeutics.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:22 |
|---|---|
| Enthalten in: |
Plant biotechnology journal - 22(2024), 4 vom: 22. März, Seite 876-891 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Merwaiss, Fernando [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 22.03.2024 Date Revised 23.03.2024 published: Print-Electronic RefSeq: MT799816.1, DQ986288 Citation Status MEDLINE |
|---|
| doi: |
10.1111/pbi.14230 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM364583037 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM364583037 | ||
| 003 | DE-627 | ||
| 005 | 20240323234756.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231226s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1111/pbi.14230 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1342.xml |
| 035 | |a (DE-627)NLM364583037 | ||
| 035 | |a (NLM)37966715 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Merwaiss, Fernando |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Plant virus-derived nanoparticles decorated with genetically encoded SARS-CoV-2 nanobodies display enhanced neutralizing activity |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 22.03.2024 | ||
| 500 | |a Date Revised 23.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a RefSeq: MT799816.1, DQ986288 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2023 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd. | ||
| 520 | |a Viral nanoparticles (VNPs) are a new class of virus-based formulations that can be used as building blocks to implement a variety of functions of potential interest in biotechnology and nanomedicine. Viral coat proteins (CP) that exhibit self-assembly properties are particularly appropriate for displaying antigens and antibodies, by generating multivalent VNPs with therapeutic and diagnostic potential. Here, we developed genetically encoded multivalent VNPs derived from two filamentous plant viruses, potato virus X (PVX) and tobacco etch virus (TEV), which were efficiently and inexpensively produced in the biofactory Nicotiana benthamiana plant. PVX and TEV-derived VNPs were decorated with two different nanobodies recognizing two different regions of the receptor-binding domain (RBD) of the SARS-CoV-2 Spike protein. The addition of different picornavirus 2A ribosomal skipping peptides between the nanobody and the CP allowed for modulating the degree of VNP decoration. Nanobody-decorated VNPs purified from N. benthamiana tissues successfully recognized the RBD antigen in enzyme-linked immunosorbent assays and showed efficient neutralization activity against pseudoviruses carrying the Spike protein. Interestingly, multivalent PVX and TEV-derived VNPs exhibited a neutralizing activity approximately one order of magnitude higher than the corresponding nanobody in a dimeric format. These properties, combined with the ability to produce VNP cocktails in the same N. benthamiana plant based on synergistic infection of the parent PVX and TEV, make these green nanomaterials an attractive alternative to standard antibodies for multiple applications in diagnosis and therapeutics | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a SARS‐CoV‐2 | |
| 650 | 4 | |a biofactory plant | |
| 650 | 4 | |a nanobody | |
| 650 | 4 | |a potato virus X | |
| 650 | 4 | |a tobacco etch virus | |
| 650 | 4 | |a viral nanoparticle | |
| 650 | 7 | |a spike protein, SARS-CoV-2 |2 NLM | |
| 650 | 7 | |a Single-Domain Antibodies |2 NLM | |
| 650 | 7 | |a Antibodies, Neutralizing |2 NLM | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 650 | 7 | |a Spike Glycoprotein, Coronavirus |2 NLM | |
| 700 | 1 | |a Lozano-Sanchez, Enrique |e verfasserin |4 aut | |
| 700 | 1 | |a Zulaica, João |e verfasserin |4 aut | |
| 700 | 1 | |a Rusu, Luciana |e verfasserin |4 aut | |
| 700 | 1 | |a Vazquez-Vilar, Marta |e verfasserin |4 aut | |
| 700 | 1 | |a Orzáez, Diego |e verfasserin |4 aut | |
| 700 | 1 | |a Rodrigo, Guillermo |e verfasserin |4 aut | |
| 700 | 1 | |a Geller, Ron |e verfasserin |4 aut | |
| 700 | 1 | |a Daròs, José-Antonio |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Plant biotechnology journal |d 2003 |g 22(2024), 4 vom: 22. März, Seite 876-891 |w (DE-627)NLM16681718X |x 1467-7652 |7 nnns |
| 773 | 1 | 8 | |g volume:22 |g year:2024 |g number:4 |g day:22 |g month:03 |g pages:876-891 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1111/pbi.14230 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 22 |j 2024 |e 4 |b 22 |c 03 |h 876-891 | ||