Human monoclonal antibodies against chikungunya virus target multiple distinct epitopes in the E1 and E2 glycoproteins
Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes persistent arthritis in a subset of human patients. We report the isolation and functional characterization of monoclonal antibodies (mAbs) from two patients infected with CHIKV in the Dominican Republic. Single B cell sorting yielded a panel of 46 human mAbs of diverse germline lineages that targeted epitopes within the E1 or E2 glycoproteins. MAbs that recognized either E1 or E2 proteins exhibited neutralizing activity. Viral escape mutations localized the binding epitopes for two E1 mAbs to sites within domain I or the linker between domains I and III; and for two E2 mAbs between the β-connector region and the B-domain. Two of the E2-specific mAbs conferred protection in vivo in a stringent lethal challenge mouse model of CHIKV infection, whereas the E1 mAbs did not. These results provide insight into human antibody response to CHIKV and identify candidate mAbs for therapeutic intervention.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2019 |
|---|---|
| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
|---|---|
| Enthalten in: |
PLoS pathogens - 15(2019), 11 vom: 08. Nov., Seite e1008061 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Quiroz, Jose A [VerfasserIn] |
|---|
| Links: |
|---|
| Anmerkungen: |
Date Completed 04.03.2020 Date Revised 24.02.2021 published: Electronic-eCollection Citation Status MEDLINE |
|---|
| doi: |
10.1371/journal.ppat.1008061 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM303017449 |
|---|
| LEADER | 01000naa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM303017449 | ||
| 003 | DE-627 | ||
| 005 | 20231225111939.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 231225s2019 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1371/journal.ppat.1008061 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1010.xml |
| 035 | |a (DE-627)NLM303017449 | ||
| 035 | |a (NLM)31697791 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Quiroz, Jose A |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Human monoclonal antibodies against chikungunya virus target multiple distinct epitopes in the E1 and E2 glycoproteins |
| 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 Completed 04.03.2020 | ||
| 500 | |a Date Revised 24.02.2021 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes persistent arthritis in a subset of human patients. We report the isolation and functional characterization of monoclonal antibodies (mAbs) from two patients infected with CHIKV in the Dominican Republic. Single B cell sorting yielded a panel of 46 human mAbs of diverse germline lineages that targeted epitopes within the E1 or E2 glycoproteins. MAbs that recognized either E1 or E2 proteins exhibited neutralizing activity. Viral escape mutations localized the binding epitopes for two E1 mAbs to sites within domain I or the linker between domains I and III; and for two E2 mAbs between the β-connector region and the B-domain. Two of the E2-specific mAbs conferred protection in vivo in a stringent lethal challenge mouse model of CHIKV infection, whereas the E1 mAbs did not. These results provide insight into human antibody response to CHIKV and identify candidate mAbs for therapeutic intervention | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Research Support, U.S. Gov't, Non-P.H.S. | |
| 650 | 7 | |a Antibodies, Monoclonal |2 NLM | |
| 650 | 7 | |a Antibodies, Neutralizing |2 NLM | |
| 650 | 7 | |a Antibodies, Viral |2 NLM | |
| 650 | 7 | |a Epitopes |2 NLM | |
| 650 | 7 | |a Glycoproteins |2 NLM | |
| 650 | 7 | |a Viral Envelope Proteins |2 NLM | |
| 700 | 1 | |a Malonis, Ryan J |e verfasserin |4 aut | |
| 700 | 1 | |a Thackray, Larissa B |e verfasserin |4 aut | |
| 700 | 1 | |a Cohen, Courtney A |e verfasserin |4 aut | |
| 700 | 1 | |a Pallesen, Jesper |e verfasserin |4 aut | |
| 700 | 1 | |a Jangra, Rohit K |e verfasserin |4 aut | |
| 700 | 1 | |a Brown, Rebecca S |e verfasserin |4 aut | |
| 700 | 1 | |a Hofmann, Daniel |e verfasserin |4 aut | |
| 700 | 1 | |a Holtsberg, Frederick W |e verfasserin |4 aut | |
| 700 | 1 | |a Shulenin, Sergey |e verfasserin |4 aut | |
| 700 | 1 | |a Nyakatura, Elisabeth K |e verfasserin |4 aut | |
| 700 | 1 | |a Durnell, Lorellin A |e verfasserin |4 aut | |
| 700 | 1 | |a Rayannavar, Vinayak |e verfasserin |4 aut | |
| 700 | 1 | |a Daily, Johanna P |e verfasserin |4 aut | |
| 700 | 1 | |a Ward, Andrew B |e verfasserin |4 aut | |
| 700 | 1 | |a Aman, M Javad |e verfasserin |4 aut | |
| 700 | 1 | |a Dye, John M |e verfasserin |4 aut | |
| 700 | 1 | |a Chandran, Kartik |e verfasserin |4 aut | |
| 700 | 1 | |a Diamond, Michael S |e verfasserin |4 aut | |
| 700 | 1 | |a Kielian, Margaret |e verfasserin |4 aut | |
| 700 | 1 | |a Lai, Jonathan R |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t PLoS pathogens |d 2005 |g 15(2019), 11 vom: 08. Nov., Seite e1008061 |w (DE-627)NLM158124782 |x 1553-7374 |7 nnns |
| 773 | 1 | 8 | |g volume:15 |g year:2019 |g number:11 |g day:08 |g month:11 |g pages:e1008061 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1371/journal.ppat.1008061 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 15 |j 2019 |e 11 |b 08 |c 11 |h e1008061 | ||