Super Potent Bispecific Llama VHH Antibodies Neutralize HIV via a Combination of gp41 and gp120 Epitopes
Broad and potent neutralizing llama single domain antibodies (VHH) against HIV-1 targeting the CD4 binding site (CD4bs) have previously been isolated upon llama immunization. Here we describe the epitopes of three additional VHH groups selected from phage libraries. The 2E7 group binds to a new linear epitope in the first heptad repeat of gp41 that is only exposed in the fusion-intermediate conformation. The 1B5 group competes with co-receptor binding and the 1F10 group interacts with the crown of the gp120 V3 loop, occluded in native Env. We present biophysical and structural details on the 2E7 interaction with gp41. In order to further increase breadth and potency, we constructed bi-specific VHH. The combination of CD4bs VHH (J3/3E3) with 2E7 group VHH enhanced strain-specific neutralization with potencies up to 1400-fold higher than the mixture of the individual VHHs. Thus, these new bivalent VHH are potent new tools to develop therapeutic approaches or microbicide intervention.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2019 |
|---|---|
| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:8 |
|---|---|
| Enthalten in: |
Antibodies (Basel, Switzerland) - 8(2019), 2 vom: 18. Juni |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Strokappe, Nika M [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
Aids |
|---|
| Anmerkungen: |
Date Revised 30.09.2020 published: Electronic Citation Status PubMed-not-MEDLINE |
|---|
| doi: |
10.3390/antib8020038 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM301528179 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM301528179 | ||
| 003 | DE-627 | ||
| 005 | 20231225104822.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.3390/antib8020038 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1005.xml |
| 035 | |a (DE-627)NLM301528179 | ||
| 035 | |a (NLM)31544844 | ||
| 035 | |a (PII)E38 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Strokappe, Nika M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Super Potent Bispecific Llama VHH Antibodies Neutralize HIV via a Combination of gp41 and gp120 Epitopes |
| 264 | 1 | |c 2019 | |
| 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 Revised 30.09.2020 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status PubMed-not-MEDLINE | ||
| 520 | |a Broad and potent neutralizing llama single domain antibodies (VHH) against HIV-1 targeting the CD4 binding site (CD4bs) have previously been isolated upon llama immunization. Here we describe the epitopes of three additional VHH groups selected from phage libraries. The 2E7 group binds to a new linear epitope in the first heptad repeat of gp41 that is only exposed in the fusion-intermediate conformation. The 1B5 group competes with co-receptor binding and the 1F10 group interacts with the crown of the gp120 V3 loop, occluded in native Env. We present biophysical and structural details on the 2E7 interaction with gp41. In order to further increase breadth and potency, we constructed bi-specific VHH. The combination of CD4bs VHH (J3/3E3) with 2E7 group VHH enhanced strain-specific neutralization with potencies up to 1400-fold higher than the mixture of the individual VHHs. Thus, these new bivalent VHH are potent new tools to develop therapeutic approaches or microbicide intervention | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Aids | |
| 650 | 4 | |a HIV | |
| 650 | 4 | |a Llama Antibodies | |
| 650 | 4 | |a bi-specific VHH | |
| 650 | 4 | |a co-crystallisation | |
| 650 | 4 | |a competition studies | |
| 650 | 4 | |a epitope mapping | |
| 650 | 4 | |a pepscan | |
| 700 | 1 | |a Hock, Miriam |e verfasserin |4 aut | |
| 700 | 1 | |a Rutten, Lucy |e verfasserin |4 aut | |
| 700 | 1 | |a Mccoy, Laura E |e verfasserin |4 aut | |
| 700 | 1 | |a Back, Jaap W |e verfasserin |4 aut | |
| 700 | 1 | |a Caillat, Christophe |e verfasserin |4 aut | |
| 700 | 1 | |a Haffke, Matthias |e verfasserin |4 aut | |
| 700 | 1 | |a Weiss, Robin A |e verfasserin |4 aut | |
| 700 | 1 | |a Weissenhorn, Winfried |e verfasserin |4 aut | |
| 700 | 1 | |a Verrips, Theo |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Antibodies (Basel, Switzerland) |d 2012 |g 8(2019), 2 vom: 18. Juni |w (DE-627)NLM236449141 |x 2073-4468 |7 nnns |
| 773 | 1 | 8 | |g volume:8 |g year:2019 |g number:2 |g day:18 |g month:06 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.3390/antib8020038 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 8 |j 2019 |e 2 |b 18 |c 06 | ||