High crossreactivity of human T cell responses between Lassa virus lineages.

Lassa virus infects hundreds of thousands of people each year across rural West Africa, resulting in a high number of cases of Lassa fever (LF), a febrile disease associated with high morbidity and significant mortality. The lack of approved treatments or interventions underscores the need for an ef...

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Main Authors: Brian M Sullivan, Saori Sakabe, Jessica N Hartnett, Nhi Ngo, Augustine Goba, Mambu Momoh, John Demby Sandi, Lansana Kanneh, Beatrice Cubitt, Selma D Garcia, Brian C Ware, Dylan Kotliar, Refugio Robles-Sikisaka, Karthik Gangavarapu, Luis Branco, Philomena Eromon, Ikponmwosa Odia, Ephraim Ogbaini-Emovon, Onikepe Folarin, Sylvanus Okogbenin, Peter O Okokhere, Christian Happi, Juan Carlos de la Torre, Pardis C Sabeti, Kristian G Andersen, Robert F Garry, Donald S Grant, John S Schieffelin, Michael B A Oldstone
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2020-03-01
Series:PLoS Pathogens
Online Access:https://doi.org/10.1371/journal.ppat.1008352
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author Brian M Sullivan
Saori Sakabe
Jessica N Hartnett
Nhi Ngo
Augustine Goba
Mambu Momoh
John Demby Sandi
Lansana Kanneh
Beatrice Cubitt
Selma D Garcia
Brian C Ware
Dylan Kotliar
Refugio Robles-Sikisaka
Karthik Gangavarapu
Luis Branco
Philomena Eromon
Ikponmwosa Odia
Ephraim Ogbaini-Emovon
Onikepe Folarin
Sylvanus Okogbenin
Peter O Okokhere
Christian Happi
Juan Carlos de la Torre
Pardis C Sabeti
Kristian G Andersen
Robert F Garry
Donald S Grant
John S Schieffelin
Michael B A Oldstone
author_facet Brian M Sullivan
Saori Sakabe
Jessica N Hartnett
Nhi Ngo
Augustine Goba
Mambu Momoh
John Demby Sandi
Lansana Kanneh
Beatrice Cubitt
Selma D Garcia
Brian C Ware
Dylan Kotliar
Refugio Robles-Sikisaka
Karthik Gangavarapu
Luis Branco
Philomena Eromon
Ikponmwosa Odia
Ephraim Ogbaini-Emovon
Onikepe Folarin
Sylvanus Okogbenin
Peter O Okokhere
Christian Happi
Juan Carlos de la Torre
Pardis C Sabeti
Kristian G Andersen
Robert F Garry
Donald S Grant
John S Schieffelin
Michael B A Oldstone
author_sort Brian M Sullivan
collection DOAJ
description Lassa virus infects hundreds of thousands of people each year across rural West Africa, resulting in a high number of cases of Lassa fever (LF), a febrile disease associated with high morbidity and significant mortality. The lack of approved treatments or interventions underscores the need for an effective vaccine. At least four viral lineages circulate in defined regions throughout West Africa with substantial interlineage nucleotide and amino acid diversity. An effective vaccine should be designed to elicit Lassa virus specific humoral and cell mediated immunity across all lineages. Most current vaccine candidates use only lineage IV antigens encoded by Lassa viruses circulating around Sierra Leone, Liberia, and Guinea but not Nigeria where lineages I-III are found. As previous infection is known to protect against disease from subsequent exposure, we sought to determine whether LF survivors from Nigeria and Sierra Leone harbor memory T cells that respond to lineage IV antigens. Our results indicate a high degree of cross-reactivity of CD8+ T cells from Nigerian LF survivors to lineage IV antigens. In addition, we identified regions within the Lassa virus glycoprotein complex and nucleoprotein that contributed to these responses while T cell epitopes were not widely conserved across our study group. These data are important for current efforts to design effective and efficient vaccine candidates that can elicit protective immunity across all Lassa virus lineages.
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spelling doaj.art-460d8324b1b64c339131f3b710e0a0b92022-12-21T19:11:11ZengPublic Library of Science (PLoS)PLoS Pathogens1553-73661553-73742020-03-01163e100835210.1371/journal.ppat.1008352High crossreactivity of human T cell responses between Lassa virus lineages.Brian M SullivanSaori SakabeJessica N HartnettNhi NgoAugustine GobaMambu MomohJohn Demby SandiLansana KannehBeatrice CubittSelma D GarciaBrian C WareDylan KotliarRefugio Robles-SikisakaKarthik GangavarapuLuis BrancoPhilomena EromonIkponmwosa OdiaEphraim Ogbaini-EmovonOnikepe FolarinSylvanus OkogbeninPeter O OkokhereChristian HappiJuan Carlos de la TorrePardis C SabetiKristian G AndersenRobert F GarryDonald S GrantJohn S SchieffelinMichael B A OldstoneLassa virus infects hundreds of thousands of people each year across rural West Africa, resulting in a high number of cases of Lassa fever (LF), a febrile disease associated with high morbidity and significant mortality. The lack of approved treatments or interventions underscores the need for an effective vaccine. At least four viral lineages circulate in defined regions throughout West Africa with substantial interlineage nucleotide and amino acid diversity. An effective vaccine should be designed to elicit Lassa virus specific humoral and cell mediated immunity across all lineages. Most current vaccine candidates use only lineage IV antigens encoded by Lassa viruses circulating around Sierra Leone, Liberia, and Guinea but not Nigeria where lineages I-III are found. As previous infection is known to protect against disease from subsequent exposure, we sought to determine whether LF survivors from Nigeria and Sierra Leone harbor memory T cells that respond to lineage IV antigens. Our results indicate a high degree of cross-reactivity of CD8+ T cells from Nigerian LF survivors to lineage IV antigens. In addition, we identified regions within the Lassa virus glycoprotein complex and nucleoprotein that contributed to these responses while T cell epitopes were not widely conserved across our study group. These data are important for current efforts to design effective and efficient vaccine candidates that can elicit protective immunity across all Lassa virus lineages.https://doi.org/10.1371/journal.ppat.1008352
spellingShingle Brian M Sullivan
Saori Sakabe
Jessica N Hartnett
Nhi Ngo
Augustine Goba
Mambu Momoh
John Demby Sandi
Lansana Kanneh
Beatrice Cubitt
Selma D Garcia
Brian C Ware
Dylan Kotliar
Refugio Robles-Sikisaka
Karthik Gangavarapu
Luis Branco
Philomena Eromon
Ikponmwosa Odia
Ephraim Ogbaini-Emovon
Onikepe Folarin
Sylvanus Okogbenin
Peter O Okokhere
Christian Happi
Juan Carlos de la Torre
Pardis C Sabeti
Kristian G Andersen
Robert F Garry
Donald S Grant
John S Schieffelin
Michael B A Oldstone
High crossreactivity of human T cell responses between Lassa virus lineages.
PLoS Pathogens
title High crossreactivity of human T cell responses between Lassa virus lineages.
title_full High crossreactivity of human T cell responses between Lassa virus lineages.
title_fullStr High crossreactivity of human T cell responses between Lassa virus lineages.
title_full_unstemmed High crossreactivity of human T cell responses between Lassa virus lineages.
title_short High crossreactivity of human T cell responses between Lassa virus lineages.
title_sort high crossreactivity of human t cell responses between lassa virus lineages
url https://doi.org/10.1371/journal.ppat.1008352
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