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Longitudinal antibody and T cell responses in Ebola virus disease survivors and contacts: an observational cohort study

BACKGROUND: The 2013–16 Ebola virus disease epidemic in west Africa caused international alarm due to its rapid and extensive spread resulting in a significant death toll and social unrest within the affected region. The large number of cases provided an opportunity to study the long-term kinetics o...

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Autores principales: Thom, Ruth, Tipton, Thomas, Strecker, Thomas, Hall, Yper, Akoi Bore, Joseph, Maes, Piet, Raymond Koundouno, Fara, Fehling, Sarah Katharina, Krähling, Verena, Steeds, Kimberley, Varghese, Anitha, Bailey, Graham, Matheson, Mary, Kouyate, Saidou, Coné, Moussa, Moussa Keita, Balla, Kouyate, Sekou, Richard Ablam, Amento, Laenen, Lies, Vergote, Valentijn, Guiver, Malcolm, Timothy, Joseph, Atkinson, Barry, Ottowell, Lisa, Richards, Kevin S, Bosworth, Andrew, Longet, Stephanie, Mellors, Jack, Pannetier, Delphine, Duraffour, Sophie, Muñoz-Fontela, César, Sow, Oumou, Koivogui, Lamine, Newman, Edmund, Becker, Stephan, Sprecher, Armand, Raoul, Herve, Hiscox, Julian, Henao-Restrepo, Ana Maria, Sakoba, Keita, Magassouba, N'Faly, Günther, Stephan, Kader Konde, Mandy, Carroll, Miles W
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier Ltd. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553754/
https://www.ncbi.nlm.nih.gov/pubmed/33065039
http://dx.doi.org/10.1016/S1473-3099(20)30736-2
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author Thom, Ruth
Tipton, Thomas
Strecker, Thomas
Hall, Yper
Akoi Bore, Joseph
Maes, Piet
Raymond Koundouno, Fara
Fehling, Sarah Katharina
Krähling, Verena
Steeds, Kimberley
Varghese, Anitha
Bailey, Graham
Matheson, Mary
Kouyate, Saidou
Coné, Moussa
Moussa Keita, Balla
Kouyate, Sekou
Richard Ablam, Amento
Laenen, Lies
Vergote, Valentijn
Guiver, Malcolm
Timothy, Joseph
Atkinson, Barry
Ottowell, Lisa
Richards, Kevin S
Bosworth, Andrew
Longet, Stephanie
Mellors, Jack
Pannetier, Delphine
Duraffour, Sophie
Muñoz-Fontela, César
Sow, Oumou
Koivogui, Lamine
Newman, Edmund
Becker, Stephan
Sprecher, Armand
Raoul, Herve
Hiscox, Julian
Henao-Restrepo, Ana Maria
Sakoba, Keita
Magassouba, N'Faly
Günther, Stephan
Kader Konde, Mandy
Carroll, Miles W
author_facet Thom, Ruth
Tipton, Thomas
Strecker, Thomas
Hall, Yper
Akoi Bore, Joseph
Maes, Piet
Raymond Koundouno, Fara
Fehling, Sarah Katharina
Krähling, Verena
Steeds, Kimberley
Varghese, Anitha
Bailey, Graham
Matheson, Mary
Kouyate, Saidou
Coné, Moussa
Moussa Keita, Balla
Kouyate, Sekou
Richard Ablam, Amento
Laenen, Lies
Vergote, Valentijn
Guiver, Malcolm
Timothy, Joseph
Atkinson, Barry
Ottowell, Lisa
Richards, Kevin S
Bosworth, Andrew
Longet, Stephanie
Mellors, Jack
Pannetier, Delphine
Duraffour, Sophie
Muñoz-Fontela, César
Sow, Oumou
Koivogui, Lamine
Newman, Edmund
Becker, Stephan
Sprecher, Armand
Raoul, Herve
Hiscox, Julian
Henao-Restrepo, Ana Maria
Sakoba, Keita
Magassouba, N'Faly
Günther, Stephan
Kader Konde, Mandy
Carroll, Miles W
author_sort Thom, Ruth
collection PubMed
description BACKGROUND: The 2013–16 Ebola virus disease epidemic in west Africa caused international alarm due to its rapid and extensive spread resulting in a significant death toll and social unrest within the affected region. The large number of cases provided an opportunity to study the long-term kinetics of Zaire ebolavirus-specific immune response of survivors in addition to known contacts of those infected with the virus. METHODS: In this observational cohort study, we worked with leaders of Ebola virus disease survivor associations in two regions of Guinea, Guéckédou and Coyah, to recruit survivors of Ebola virus disease, contacts from households of individuals known to have had Ebola virus disease, and individuals who were not knowingly associated with infected individuals or had not had Ebola virus disease symptoms to serve as negative controls. We did Zaire ebolavirus glycoprotein-specific T cell analysis on peripheral blood mononuclear cells (PBMCs) on location in Guinea and transported plasma and PBMCs back to Europe for antibody quantification by ELISA, functional neutralising antibody analysis using live Zaire ebolavirus, and T cell phenotype studies. We report on the longitudinal cellular and humoral response among Ebola virus disease survivors and highlight potentially paucisymptomatic infection. FINDINGS: We recruited 117 survivors of Ebola virus disease, 66 contacts, and 23 negative controls. The mean neutralising antibody titre among the Ebola virus disease survivors 3–14 months after infection was 1/174 (95% CI 1/136—1/223). Individual results varied greatly from 1/10 to more than 1/1000 but were on average ten times greater than that induced after 1 month by single dose Ebola virus vaccines. Following reactivation with glycoprotein peptide, the mean T cell responses among 116 Ebola virus disease survivors as measured by ELISpot was 305 spot-forming units (95% CI 257–353). The dominant CD8+ polyfunctional T cell phenotype, as measured among 53 Ebola virus disease survivors, was interferon γ+, tumour necrosis factor+, interleukin-2–, and the mean response was 0·046% of total CD8+ T cells (95% CI 0·021–0·071). Additionally, both neutralising antibody and T cell responses were detected in six (9%) of 66 Ebola virus disease contacts. We also noted that four (3%) of 117 individuals with Ebola virus disease infections did not have circulating Ebola virus-specific antibodies 3 months after infection. INTERPRETATION: The continuous high titre of neutralising antibodies and increased T cell response might support the concept of long-term protective immunity in survivors. The existence of antibody and T cell responses in contacts of individuals with Ebola virus disease adds further evidence to the existence of sub-clinical Ebola virus infection. FUNDING: US Food & Drug Administration, Horizon 2020 EU EVIDENT, Wellcome, UK Department for International Development.
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spelling pubmed-75537542020-10-14 Longitudinal antibody and T cell responses in Ebola virus disease survivors and contacts: an observational cohort study Thom, Ruth Tipton, Thomas Strecker, Thomas Hall, Yper Akoi Bore, Joseph Maes, Piet Raymond Koundouno, Fara Fehling, Sarah Katharina Krähling, Verena Steeds, Kimberley Varghese, Anitha Bailey, Graham Matheson, Mary Kouyate, Saidou Coné, Moussa Moussa Keita, Balla Kouyate, Sekou Richard Ablam, Amento Laenen, Lies Vergote, Valentijn Guiver, Malcolm Timothy, Joseph Atkinson, Barry Ottowell, Lisa Richards, Kevin S Bosworth, Andrew Longet, Stephanie Mellors, Jack Pannetier, Delphine Duraffour, Sophie Muñoz-Fontela, César Sow, Oumou Koivogui, Lamine Newman, Edmund Becker, Stephan Sprecher, Armand Raoul, Herve Hiscox, Julian Henao-Restrepo, Ana Maria Sakoba, Keita Magassouba, N'Faly Günther, Stephan Kader Konde, Mandy Carroll, Miles W Lancet Infect Dis Articles BACKGROUND: The 2013–16 Ebola virus disease epidemic in west Africa caused international alarm due to its rapid and extensive spread resulting in a significant death toll and social unrest within the affected region. The large number of cases provided an opportunity to study the long-term kinetics of Zaire ebolavirus-specific immune response of survivors in addition to known contacts of those infected with the virus. METHODS: In this observational cohort study, we worked with leaders of Ebola virus disease survivor associations in two regions of Guinea, Guéckédou and Coyah, to recruit survivors of Ebola virus disease, contacts from households of individuals known to have had Ebola virus disease, and individuals who were not knowingly associated with infected individuals or had not had Ebola virus disease symptoms to serve as negative controls. We did Zaire ebolavirus glycoprotein-specific T cell analysis on peripheral blood mononuclear cells (PBMCs) on location in Guinea and transported plasma and PBMCs back to Europe for antibody quantification by ELISA, functional neutralising antibody analysis using live Zaire ebolavirus, and T cell phenotype studies. We report on the longitudinal cellular and humoral response among Ebola virus disease survivors and highlight potentially paucisymptomatic infection. FINDINGS: We recruited 117 survivors of Ebola virus disease, 66 contacts, and 23 negative controls. The mean neutralising antibody titre among the Ebola virus disease survivors 3–14 months after infection was 1/174 (95% CI 1/136—1/223). Individual results varied greatly from 1/10 to more than 1/1000 but were on average ten times greater than that induced after 1 month by single dose Ebola virus vaccines. Following reactivation with glycoprotein peptide, the mean T cell responses among 116 Ebola virus disease survivors as measured by ELISpot was 305 spot-forming units (95% CI 257–353). The dominant CD8+ polyfunctional T cell phenotype, as measured among 53 Ebola virus disease survivors, was interferon γ+, tumour necrosis factor+, interleukin-2–, and the mean response was 0·046% of total CD8+ T cells (95% CI 0·021–0·071). Additionally, both neutralising antibody and T cell responses were detected in six (9%) of 66 Ebola virus disease contacts. We also noted that four (3%) of 117 individuals with Ebola virus disease infections did not have circulating Ebola virus-specific antibodies 3 months after infection. INTERPRETATION: The continuous high titre of neutralising antibodies and increased T cell response might support the concept of long-term protective immunity in survivors. The existence of antibody and T cell responses in contacts of individuals with Ebola virus disease adds further evidence to the existence of sub-clinical Ebola virus infection. FUNDING: US Food & Drug Administration, Horizon 2020 EU EVIDENT, Wellcome, UK Department for International Development. Elsevier Ltd. 2020-10-13 /pmc/articles/PMC7553754/ /pubmed/33065039 http://dx.doi.org/10.1016/S1473-3099(20)30736-2 Text en © 2020 Elsevier Ltd. All rights reserved. Since January 2020 Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.
spellingShingle Articles
Thom, Ruth
Tipton, Thomas
Strecker, Thomas
Hall, Yper
Akoi Bore, Joseph
Maes, Piet
Raymond Koundouno, Fara
Fehling, Sarah Katharina
Krähling, Verena
Steeds, Kimberley
Varghese, Anitha
Bailey, Graham
Matheson, Mary
Kouyate, Saidou
Coné, Moussa
Moussa Keita, Balla
Kouyate, Sekou
Richard Ablam, Amento
Laenen, Lies
Vergote, Valentijn
Guiver, Malcolm
Timothy, Joseph
Atkinson, Barry
Ottowell, Lisa
Richards, Kevin S
Bosworth, Andrew
Longet, Stephanie
Mellors, Jack
Pannetier, Delphine
Duraffour, Sophie
Muñoz-Fontela, César
Sow, Oumou
Koivogui, Lamine
Newman, Edmund
Becker, Stephan
Sprecher, Armand
Raoul, Herve
Hiscox, Julian
Henao-Restrepo, Ana Maria
Sakoba, Keita
Magassouba, N'Faly
Günther, Stephan
Kader Konde, Mandy
Carroll, Miles W
Longitudinal antibody and T cell responses in Ebola virus disease survivors and contacts: an observational cohort study
title Longitudinal antibody and T cell responses in Ebola virus disease survivors and contacts: an observational cohort study
title_full Longitudinal antibody and T cell responses in Ebola virus disease survivors and contacts: an observational cohort study
title_fullStr Longitudinal antibody and T cell responses in Ebola virus disease survivors and contacts: an observational cohort study
title_full_unstemmed Longitudinal antibody and T cell responses in Ebola virus disease survivors and contacts: an observational cohort study
title_short Longitudinal antibody and T cell responses in Ebola virus disease survivors and contacts: an observational cohort study
title_sort longitudinal antibody and t cell responses in ebola virus disease survivors and contacts: an observational cohort study
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553754/
https://www.ncbi.nlm.nih.gov/pubmed/33065039
http://dx.doi.org/10.1016/S1473-3099(20)30736-2
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