The first human epitope map of the alphaviral E1 and E2 proteins reveals a new E2 epitope with significant virus neutralizing activity.
Venezuelan equine encephalitis virus (VEEV) is responsible for VEE epidemics that occur in South and Central America and the U.S. The VEEV envelope contains two glycoproteins E1 (mediates cell membrane fusion) and E2 (binds receptor and elicits virus neutralizing antibodies). Previously we construct...
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ftdoajarticles:oai:doaj.org/article:05da1765fd2245db852ae49bd17d2266 2023-05-15T15:18:17+02:00 The first human epitope map of the alphaviral E1 and E2 proteins reveals a new E2 epitope with significant virus neutralizing activity. Ann R Hunt Shana Frederickson Toshiaki Maruyama John T Roehrig Carol D Blair 2010-07-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0000739 https://doaj.org/article/05da1765fd2245db852ae49bd17d2266 EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC2903468?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0000739 https://doaj.org/article/05da1765fd2245db852ae49bd17d2266 PLoS Neglected Tropical Diseases, Vol 4, Iss 7, p e739 (2010) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2010 ftdoajarticles https://doi.org/10.1371/journal.pntd.0000739 2022-12-31T13:35:33Z Venezuelan equine encephalitis virus (VEEV) is responsible for VEE epidemics that occur in South and Central America and the U.S. The VEEV envelope contains two glycoproteins E1 (mediates cell membrane fusion) and E2 (binds receptor and elicits virus neutralizing antibodies). Previously we constructed E1 and E2 epitope maps using murine monoclonal antibodies (mMAbs). Six E2 epitopes (E2(c,d,e,f,g,h)) bound VEEV-neutralizing antibody and mapped to amino acids (aa) 182-207. Nothing is known about the human antibody repertoire to VEEV or epitopes that engage human virus-neutralizing antibodies. There is no specific treatment for VEE; however virus-neutralizing mMAbs are potent protective and therapeutic agents for mice challenged with VEEV by either peripheral or aerosol routes. Therefore, fully human MAbs (hMAbs) with virus-neutralizing activity should be useful for prevention or clinical treatment of human VEE.We used phage-display to isolate VEEV-specific hFabs from human bone marrow donors. These hFabs were characterized by sequencing, specificity testing, VEEV subtype cross-reactivity using indirect ELISA, and in vitro virus neutralization capacity. One E2-specific neutralizing hFAb, F5n, was converted into IgG, and its binding site was identified using competitive ELISA with mMAbs and by preparing and sequencing antibody neutralization-escape variants.Using 11 VEEV-reactive hFabs we constructed the first human epitope map for the alphaviral surface proteins E1 and E2. We identified an important neutralization-associated epitope unique to the human immune response, E2 aa115-119. Using a 9 A resolution cryo-electron microscopy map of the Sindbis virus E2 protein, we showed the probable surface location of this human VEEV epitope.The VEEV-neutralizing capacity of the hMAb F5 nIgG is similar to that exhibited by the humanized mMAb Hy4 IgG. The Hy4 IgG has been shown to limit VEEV infection in mice both prophylactically and therapeutically. Administration of a cocktail of F5n and Hy4 IgGs, which bind to different ... Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Nigg ENVELOPE(-44.833,-44.833,-60.700,-60.700) PLoS Neglected Tropical Diseases 4 7 e739 |
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ftdoajarticles |
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English |
topic |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
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Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 Ann R Hunt Shana Frederickson Toshiaki Maruyama John T Roehrig Carol D Blair The first human epitope map of the alphaviral E1 and E2 proteins reveals a new E2 epitope with significant virus neutralizing activity. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Venezuelan equine encephalitis virus (VEEV) is responsible for VEE epidemics that occur in South and Central America and the U.S. The VEEV envelope contains two glycoproteins E1 (mediates cell membrane fusion) and E2 (binds receptor and elicits virus neutralizing antibodies). Previously we constructed E1 and E2 epitope maps using murine monoclonal antibodies (mMAbs). Six E2 epitopes (E2(c,d,e,f,g,h)) bound VEEV-neutralizing antibody and mapped to amino acids (aa) 182-207. Nothing is known about the human antibody repertoire to VEEV or epitopes that engage human virus-neutralizing antibodies. There is no specific treatment for VEE; however virus-neutralizing mMAbs are potent protective and therapeutic agents for mice challenged with VEEV by either peripheral or aerosol routes. Therefore, fully human MAbs (hMAbs) with virus-neutralizing activity should be useful for prevention or clinical treatment of human VEE.We used phage-display to isolate VEEV-specific hFabs from human bone marrow donors. These hFabs were characterized by sequencing, specificity testing, VEEV subtype cross-reactivity using indirect ELISA, and in vitro virus neutralization capacity. One E2-specific neutralizing hFAb, F5n, was converted into IgG, and its binding site was identified using competitive ELISA with mMAbs and by preparing and sequencing antibody neutralization-escape variants.Using 11 VEEV-reactive hFabs we constructed the first human epitope map for the alphaviral surface proteins E1 and E2. We identified an important neutralization-associated epitope unique to the human immune response, E2 aa115-119. Using a 9 A resolution cryo-electron microscopy map of the Sindbis virus E2 protein, we showed the probable surface location of this human VEEV epitope.The VEEV-neutralizing capacity of the hMAb F5 nIgG is similar to that exhibited by the humanized mMAb Hy4 IgG. The Hy4 IgG has been shown to limit VEEV infection in mice both prophylactically and therapeutically. Administration of a cocktail of F5n and Hy4 IgGs, which bind to different ... |
format |
Article in Journal/Newspaper |
author |
Ann R Hunt Shana Frederickson Toshiaki Maruyama John T Roehrig Carol D Blair |
author_facet |
Ann R Hunt Shana Frederickson Toshiaki Maruyama John T Roehrig Carol D Blair |
author_sort |
Ann R Hunt |
title |
The first human epitope map of the alphaviral E1 and E2 proteins reveals a new E2 epitope with significant virus neutralizing activity. |
title_short |
The first human epitope map of the alphaviral E1 and E2 proteins reveals a new E2 epitope with significant virus neutralizing activity. |
title_full |
The first human epitope map of the alphaviral E1 and E2 proteins reveals a new E2 epitope with significant virus neutralizing activity. |
title_fullStr |
The first human epitope map of the alphaviral E1 and E2 proteins reveals a new E2 epitope with significant virus neutralizing activity. |
title_full_unstemmed |
The first human epitope map of the alphaviral E1 and E2 proteins reveals a new E2 epitope with significant virus neutralizing activity. |
title_sort |
first human epitope map of the alphaviral e1 and e2 proteins reveals a new e2 epitope with significant virus neutralizing activity. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2010 |
url |
https://doi.org/10.1371/journal.pntd.0000739 https://doaj.org/article/05da1765fd2245db852ae49bd17d2266 |
long_lat |
ENVELOPE(-44.833,-44.833,-60.700,-60.700) |
geographic |
Arctic Nigg |
geographic_facet |
Arctic Nigg |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 4, Iss 7, p e739 (2010) |
op_relation |
http://europepmc.org/articles/PMC2903468?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0000739 https://doaj.org/article/05da1765fd2245db852ae49bd17d2266 |
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https://doi.org/10.1371/journal.pntd.0000739 |
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PLoS Neglected Tropical Diseases |
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4 |
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7 |
container_start_page |
e739 |
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1766348487215022080 |