Identifying the Role of E2 Domains on Alphavirus Neutralization and Protective Immune Responses.
Chikungunya virus (CHIKV) and other alphaviruses are the etiologic agents of numerous diseases in both humans and animals. Despite this, the viral mediators of protective immunity against alphaviruses are poorly understood, highlighted by the lack of a licensed human vaccine for any member of this v...
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ftdoajarticles:oai:doaj.org/article:ab28f6596a3f41ca81d3a66cbfefeb3f 2023-05-15T15:10:43+02:00 Identifying the Role of E2 Domains on Alphavirus Neutralization and Protective Immune Responses. James Weger-Lucarelli Matthew T Aliota Attapon Kamlangdee Jorge E Osorio 2015-01-01T00:00:00Z https://doi.org/10.1371/journal.pntd.0004163 https://doaj.org/article/ab28f6596a3f41ca81d3a66cbfefeb3f EN eng Public Library of Science (PLoS) http://europepmc.org/articles/PMC4608762?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004163 https://doaj.org/article/ab28f6596a3f41ca81d3a66cbfefeb3f PLoS Neglected Tropical Diseases, Vol 9, Iss 10, p e0004163 (2015) Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 article 2015 ftdoajarticles https://doi.org/10.1371/journal.pntd.0004163 2022-12-31T08:44:01Z Chikungunya virus (CHIKV) and other alphaviruses are the etiologic agents of numerous diseases in both humans and animals. Despite this, the viral mediators of protective immunity against alphaviruses are poorly understood, highlighted by the lack of a licensed human vaccine for any member of this virus genus. The alphavirus E2, the receptor-binding envelope protein, is considered to be the predominant target of the protective host immune response. Although envelope protein domains have been studied for vaccine and neutralization in flaviviruses, their role in alphaviruses is less characterized. Here, we describe the role of the alphavirus E2 domains in neutralization and protection through the use of chimeric viruses.Four chimeric viruses were constructed in which individual E2 domains of CHIKV were replaced with the corresponding domain from Semliki Forest virus (SFV) (ΔDomA/ΔDomB/ΔDomC/ ΔDomA+B). Vaccination studies in mice (both live and inactivated virus) revealed that domain B was the primary determinant of neutralization. Neutralization studies with CHIKV immune serum from humans were consistent with mouse studies, as ΔDomB was poorly neutralized.Using chimeric viruses, it was determined that the alphavirus E2 domain B was the critical target of neutralizing antibodies in both mice and humans. Therefore, chimeric viruses may have more relevance for vaccine discovery than peptide-based approaches, which only detect linear epitopes. This study provides new insight into the role of alphavirus E2 domains on neutralization determinants and may be useful for the design of novel therapeutic technologies. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic PLOS Neglected Tropical Diseases 9 10 e0004163 |
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Open Polar |
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Directory of Open Access Journals: DOAJ Articles |
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ftdoajarticles |
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English |
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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 James Weger-Lucarelli Matthew T Aliota Attapon Kamlangdee Jorge E Osorio Identifying the Role of E2 Domains on Alphavirus Neutralization and Protective Immune Responses. |
topic_facet |
Arctic medicine. Tropical medicine RC955-962 Public aspects of medicine RA1-1270 |
description |
Chikungunya virus (CHIKV) and other alphaviruses are the etiologic agents of numerous diseases in both humans and animals. Despite this, the viral mediators of protective immunity against alphaviruses are poorly understood, highlighted by the lack of a licensed human vaccine for any member of this virus genus. The alphavirus E2, the receptor-binding envelope protein, is considered to be the predominant target of the protective host immune response. Although envelope protein domains have been studied for vaccine and neutralization in flaviviruses, their role in alphaviruses is less characterized. Here, we describe the role of the alphavirus E2 domains in neutralization and protection through the use of chimeric viruses.Four chimeric viruses were constructed in which individual E2 domains of CHIKV were replaced with the corresponding domain from Semliki Forest virus (SFV) (ΔDomA/ΔDomB/ΔDomC/ ΔDomA+B). Vaccination studies in mice (both live and inactivated virus) revealed that domain B was the primary determinant of neutralization. Neutralization studies with CHIKV immune serum from humans were consistent with mouse studies, as ΔDomB was poorly neutralized.Using chimeric viruses, it was determined that the alphavirus E2 domain B was the critical target of neutralizing antibodies in both mice and humans. Therefore, chimeric viruses may have more relevance for vaccine discovery than peptide-based approaches, which only detect linear epitopes. This study provides new insight into the role of alphavirus E2 domains on neutralization determinants and may be useful for the design of novel therapeutic technologies. |
format |
Article in Journal/Newspaper |
author |
James Weger-Lucarelli Matthew T Aliota Attapon Kamlangdee Jorge E Osorio |
author_facet |
James Weger-Lucarelli Matthew T Aliota Attapon Kamlangdee Jorge E Osorio |
author_sort |
James Weger-Lucarelli |
title |
Identifying the Role of E2 Domains on Alphavirus Neutralization and Protective Immune Responses. |
title_short |
Identifying the Role of E2 Domains on Alphavirus Neutralization and Protective Immune Responses. |
title_full |
Identifying the Role of E2 Domains on Alphavirus Neutralization and Protective Immune Responses. |
title_fullStr |
Identifying the Role of E2 Domains on Alphavirus Neutralization and Protective Immune Responses. |
title_full_unstemmed |
Identifying the Role of E2 Domains on Alphavirus Neutralization and Protective Immune Responses. |
title_sort |
identifying the role of e2 domains on alphavirus neutralization and protective immune responses. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2015 |
url |
https://doi.org/10.1371/journal.pntd.0004163 https://doaj.org/article/ab28f6596a3f41ca81d3a66cbfefeb3f |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
PLoS Neglected Tropical Diseases, Vol 9, Iss 10, p e0004163 (2015) |
op_relation |
http://europepmc.org/articles/PMC4608762?pdf=render https://doaj.org/toc/1935-2727 https://doaj.org/toc/1935-2735 1935-2727 1935-2735 doi:10.1371/journal.pntd.0004163 https://doaj.org/article/ab28f6596a3f41ca81d3a66cbfefeb3f |
op_doi |
https://doi.org/10.1371/journal.pntd.0004163 |
container_title |
PLOS Neglected Tropical Diseases |
container_volume |
9 |
container_issue |
10 |
container_start_page |
e0004163 |
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1766341690348535808 |