Ebola virus antibody decay–stimulation in a high proportion of survivors

the Ebola-CP Consortium

doi:10.1038/s41586-020-03146-y

Ebola virus antibody decay–stimulation in a high proportion of survivors

the Ebola-CP Consortium

Research output: Contribution to journal › Article › peer-review

29 Citations (Scopus)

Abstract

Neutralizing antibody function provides a foundation for the efficacy of vaccines and therapies^1–3. Here, using a robust in vitro Ebola virus (EBOV) pseudo-particle infection assay and a well-defined set of solid-phase assays, we describe a wide spectrum of antibody responses in a cohort of healthy survivors of the Sierra Leone EBOV outbreak of 2013–2016. Pseudo-particle virus-neutralizing antibodies correlated with total anti-EBOV reactivity and neutralizing antibodies against live EBOV. Variant EBOV glycoproteins (1995 and 2014 strains) were similarly neutralized. During longitudinal follow-up, antibody responses fluctuated in a ‘decay–stimulation–decay’ pattern that suggests de novo restimulation by EBOV antigens after recovery. A pharmacodynamic model of antibody reactivity identified a decay half-life of 77–100 days and a doubling time of 46–86 days in a high proportion of survivors. The highest antibody reactivity was observed around 200 days after an individual had recovered. The model suggests that EBOV antibody reactivity declines over 0.5–2 years after recovery. In a high proportion of healthy survivors, antibody responses undergo rapid restimulation. Vigilant follow-up of survivors and possible elective de novo antigenic stimulation by vaccine immunization should be considered in order to prevent EBOV viral recrudescence in recovering individuals and thereby to mitigate the potential risk of reseeding an outbreak.

Original language	English
Pages (from-to)	468-472
Number of pages	22
Journal	Nature
Volume	590
Issue number	7846
Early online date	27 Jan 2021
DOIs	https://doi.org/10.1038/s41586-020-03146-y
Publication status	Published - 18 Feb 2021

Bibliographical note

Funding Information:
Acknowledgements We thank colleagues variously for their support and encouragement: the Sierra Leone Association of Ebola Survivors (Freetown, Sierra Leone); the members of the Convalescent Products and Allied Therapy Intervention Technical Committee; the Research Ethics Committee and the Pharmacy Board Committee (all Ministry of Health and Sanitation, Republic of Sierra Leone); staff in Virus Reference Department Public Health England for handling and clearing samples from quarantine; G. McCann and L. Matthews for project management; I. Bates for expertise in strengthening transfusion services; W. A. Brooks; M. P. Kieny; C. Burm and D. Arango; N. F. Walker; A. Jones; colleagues from the World Health Organization (WHO); and the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). Proofreading support provided by M. de Baar and graphical support provided by S. Yee. The study “Convalescent plasma for early Ebola virus disease in Sierra Leone (Ebola CP)” (ISRCTN13990511 and PACTR201602001355272) was supported by the Wellcome Trust (Award 106491) and Bill and Melinda Gates Foundation; Public Health England Ebola Emergency Response; and the Blood Safety Programme, National Health Service Blood and Transplant. J.T.S. was supported by the Wellcome Trust. M.G.S. and J.T.S. were supported by the UK National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections at the University of Liverpool. The funders had no role in the collection and analysis of the samples, in the interpretation of data, in writing the report, or in the decision to submit the paper for publication.

Keywords

CONVALESCENT PLASMA
EFFICACY
FUSION INHIBITOR T-20
NEUTRALIZATION
POPULATION PHARMACOKINETICS
REPLICATION
SIERRA-LEONE
SIMULATION
TYPE-1
VACCINE

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1038/s41586-020-03146-y

Cite this

@article{95e67abc37ca415daabb612fb22b3f2f,

title = "Ebola virus antibody decay–stimulation in a high proportion of survivors",

abstract = "Neutralizing antibody function provides a foundation for the efficacy of vaccines and therapies1–3. Here, using a robust in vitro Ebola virus (EBOV) pseudo-particle infection assay and a well-defined set of solid-phase assays, we describe a wide spectrum of antibody responses in a cohort of healthy survivors of the Sierra Leone EBOV outbreak of 2013–2016. Pseudo-particle virus-neutralizing antibodies correlated with total anti-EBOV reactivity and neutralizing antibodies against live EBOV. Variant EBOV glycoproteins (1995 and 2014 strains) were similarly neutralized. During longitudinal follow-up, antibody responses fluctuated in a {\textquoteleft}decay–stimulation–decay{\textquoteright} pattern that suggests de novo restimulation by EBOV antigens after recovery. A pharmacodynamic model of antibody reactivity identified a decay half-life of 77–100 days and a doubling time of 46–86 days in a high proportion of survivors. The highest antibody reactivity was observed around 200 days after an individual had recovered. The model suggests that EBOV antibody reactivity declines over 0.5–2 years after recovery. In a high proportion of healthy survivors, antibody responses undergo rapid restimulation. Vigilant follow-up of survivors and possible elective de novo antigenic stimulation by vaccine immunization should be considered in order to prevent EBOV viral recrudescence in recovering individuals and thereby to mitigate the potential risk of reseeding an outbreak.",

keywords = "CONVALESCENT PLASMA, EFFICACY, FUSION INHIBITOR T-20, NEUTRALIZATION, POPULATION PHARMACOKINETICS, REPLICATION, SIERRA-LEONE, SIMULATION, TYPE-1, VACCINE",

author = "{the Ebola-CP Consortium} and Charlene Adaken and Scott, {Janet T.} and Raman Sharma and Robin Gopal and Steven Dicks and Saidia Niazi and Samreen Ijaz and Tansy Edwards and Smith, {Catherine C.} and Cole, {Christine P.} and Philip Kamara and Osman Kargbo and Doughty, {Heidi A.} and {van Griensven}, Johan and Horby, {Peter W.} and Gevao, {Sahr M.} and Foday Sahr and Semple, {M. G.} and Scott, {J. T.} and Gevao, {S. M.} and F. Sahr and Cole, {C. P.} and J. Russell and S. Baker and O. Kargbo and P. Kamara and M. Lado and Brown, {C. S.} and B. Conton and {van Griensven}, J. and R. Ravinetto and Y. Claeys and Tedder, {R. S.} and Brooks, {T. J.G.} and Smith, {C. C.} and Doughty, {H. A.} and Saez, {A. Mari} and Kelly, {A. H.} and Baillie, {J. K.} and N. Shindo and D. Pfeifer and Hoover, {D. L.} and Fischer, {W. A.} and Wohl, {D. A.} and Thielman, {N. M.} and Horby, {P. W.} and L. Merson and Smith, {P. G.} and T. Edwards",

note = "Funding Information: Acknowledgements We thank colleagues variously for their support and encouragement: the Sierra Leone Association of Ebola Survivors (Freetown, Sierra Leone); the members of the Convalescent Products and Allied Therapy Intervention Technical Committee; the Research Ethics Committee and the Pharmacy Board Committee (all Ministry of Health and Sanitation, Republic of Sierra Leone); staff in Virus Reference Department Public Health England for handling and clearing samples from quarantine; G. McCann and L. Matthews for project management; I. Bates for expertise in strengthening transfusion services; W. A. Brooks; M. P. Kieny; C. Burm and D. Arango; N. F. Walker; A. Jones; colleagues from the World Health Organization (WHO); and the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). Proofreading support provided by M. de Baar and graphical support provided by S. Yee. The study “Convalescent plasma for early Ebola virus disease in Sierra Leone (Ebola CP)” (ISRCTN13990511 and PACTR201602001355272) was supported by the Wellcome Trust (Award 106491) and Bill and Melinda Gates Foundation; Public Health England Ebola Emergency Response; and the Blood Safety Programme, National Health Service Blood and Transplant. J.T.S. was supported by the Wellcome Trust. M.G.S. and J.T.S. were supported by the UK National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections at the University of Liverpool. The funders had no role in the collection and analysis of the samples, in the interpretation of data, in writing the report, or in the decision to submit the paper for publication.",

year = "2021",

month = feb,

day = "18",

doi = "10.1038/s41586-020-03146-y",

language = "English",

volume = "590",

pages = "468--472",

journal = "Nature",

issn = "0028-0836",

publisher = "Nature Research",

number = "7846",

}

TY - JOUR

T1 - Ebola virus antibody decay–stimulation in a high proportion of survivors

AU - the Ebola-CP Consortium

AU - Adaken, Charlene

AU - Scott, Janet T.

AU - Sharma, Raman

AU - Gopal, Robin

AU - Dicks, Steven

AU - Niazi, Saidia

AU - Ijaz, Samreen

AU - Edwards, Tansy

AU - Smith, Catherine C.

AU - Cole, Christine P.

AU - Kamara, Philip

AU - Kargbo, Osman

AU - Doughty, Heidi A.

AU - van Griensven, Johan

AU - Horby, Peter W.

AU - Gevao, Sahr M.

AU - Sahr, Foday

AU - Semple, M. G.

AU - Scott, J. T.

AU - Gevao, S. M.

AU - Sahr, F.

AU - Cole, C. P.

AU - Russell, J.

AU - Baker, S.

AU - Kargbo, O.

AU - Kamara, P.

AU - Lado, M.

AU - Brown, C. S.

AU - Conton, B.

AU - van Griensven, J.

AU - Ravinetto, R.

AU - Claeys, Y.

AU - Tedder, R. S.

AU - Brooks, T. J.G.

AU - Smith, C. C.

AU - Doughty, H. A.

AU - Saez, A. Mari

AU - Kelly, A. H.

AU - Baillie, J. K.

AU - Shindo, N.

AU - Pfeifer, D.

AU - Hoover, D. L.

AU - Fischer, W. A.

AU - Wohl, D. A.

AU - Thielman, N. M.

AU - Horby, P. W.

AU - Merson, L.

AU - Smith, P. G.

AU - Edwards, T.

N1 - Funding Information: Acknowledgements We thank colleagues variously for their support and encouragement: the Sierra Leone Association of Ebola Survivors (Freetown, Sierra Leone); the members of the Convalescent Products and Allied Therapy Intervention Technical Committee; the Research Ethics Committee and the Pharmacy Board Committee (all Ministry of Health and Sanitation, Republic of Sierra Leone); staff in Virus Reference Department Public Health England for handling and clearing samples from quarantine; G. McCann and L. Matthews for project management; I. Bates for expertise in strengthening transfusion services; W. A. Brooks; M. P. Kieny; C. Burm and D. Arango; N. F. Walker; A. Jones; colleagues from the World Health Organization (WHO); and the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC). Proofreading support provided by M. de Baar and graphical support provided by S. Yee. The study “Convalescent plasma for early Ebola virus disease in Sierra Leone (Ebola CP)” (ISRCTN13990511 and PACTR201602001355272) was supported by the Wellcome Trust (Award 106491) and Bill and Melinda Gates Foundation; Public Health England Ebola Emergency Response; and the Blood Safety Programme, National Health Service Blood and Transplant. J.T.S. was supported by the Wellcome Trust. M.G.S. and J.T.S. were supported by the UK National Institute for Health Research Health Protection Research Unit in Emerging and Zoonotic Infections at the University of Liverpool. The funders had no role in the collection and analysis of the samples, in the interpretation of data, in writing the report, or in the decision to submit the paper for publication.

PY - 2021/2/18

Y1 - 2021/2/18

N2 - Neutralizing antibody function provides a foundation for the efficacy of vaccines and therapies1–3. Here, using a robust in vitro Ebola virus (EBOV) pseudo-particle infection assay and a well-defined set of solid-phase assays, we describe a wide spectrum of antibody responses in a cohort of healthy survivors of the Sierra Leone EBOV outbreak of 2013–2016. Pseudo-particle virus-neutralizing antibodies correlated with total anti-EBOV reactivity and neutralizing antibodies against live EBOV. Variant EBOV glycoproteins (1995 and 2014 strains) were similarly neutralized. During longitudinal follow-up, antibody responses fluctuated in a ‘decay–stimulation–decay’ pattern that suggests de novo restimulation by EBOV antigens after recovery. A pharmacodynamic model of antibody reactivity identified a decay half-life of 77–100 days and a doubling time of 46–86 days in a high proportion of survivors. The highest antibody reactivity was observed around 200 days after an individual had recovered. The model suggests that EBOV antibody reactivity declines over 0.5–2 years after recovery. In a high proportion of healthy survivors, antibody responses undergo rapid restimulation. Vigilant follow-up of survivors and possible elective de novo antigenic stimulation by vaccine immunization should be considered in order to prevent EBOV viral recrudescence in recovering individuals and thereby to mitigate the potential risk of reseeding an outbreak.

AB - Neutralizing antibody function provides a foundation for the efficacy of vaccines and therapies1–3. Here, using a robust in vitro Ebola virus (EBOV) pseudo-particle infection assay and a well-defined set of solid-phase assays, we describe a wide spectrum of antibody responses in a cohort of healthy survivors of the Sierra Leone EBOV outbreak of 2013–2016. Pseudo-particle virus-neutralizing antibodies correlated with total anti-EBOV reactivity and neutralizing antibodies against live EBOV. Variant EBOV glycoproteins (1995 and 2014 strains) were similarly neutralized. During longitudinal follow-up, antibody responses fluctuated in a ‘decay–stimulation–decay’ pattern that suggests de novo restimulation by EBOV antigens after recovery. A pharmacodynamic model of antibody reactivity identified a decay half-life of 77–100 days and a doubling time of 46–86 days in a high proportion of survivors. The highest antibody reactivity was observed around 200 days after an individual had recovered. The model suggests that EBOV antibody reactivity declines over 0.5–2 years after recovery. In a high proportion of healthy survivors, antibody responses undergo rapid restimulation. Vigilant follow-up of survivors and possible elective de novo antigenic stimulation by vaccine immunization should be considered in order to prevent EBOV viral recrudescence in recovering individuals and thereby to mitigate the potential risk of reseeding an outbreak.

KW - CONVALESCENT PLASMA

KW - EFFICACY

KW - FUSION INHIBITOR T-20

KW - NEUTRALIZATION

KW - POPULATION PHARMACOKINETICS

KW - REPLICATION

KW - SIERRA-LEONE

KW - SIMULATION

KW - TYPE-1

KW - VACCINE

UR - http://www.scopus.com/inward/record.url?scp=85099969697&partnerID=8YFLogxK

U2 - 10.1038/s41586-020-03146-y

DO - 10.1038/s41586-020-03146-y

M3 - Article

AN - SCOPUS:85099969697

SN - 0028-0836

VL - 590

SP - 468

EP - 472

JO - Nature

JF - Nature

IS - 7846

ER -

Ebola virus antibody decay–stimulation in a high proportion of survivors

Abstract

Bibliographical note

Keywords

UN SDGs

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