Safety and immunogenicity of the rVSV∆G-ZEBOV-GP Ebola virus vaccine candidate in healthy adults: a phase 1b randomised, multicentre, double-blind, placebo-controlled, dose-response study

D. Gray Heppner, Tracy L. Kemp, Brian K. Martin, William J. Ramsey, Richard Nichols, Emily J. Dasen, Charles J. Link, Rituparna Das, Zhi Jin Xu, Eric A. Sheldon, Teresa A. Nowak, Thomas P. Monath, J. Fusco, J. Crowell, J. Creager, R. Klein, E. Gerstenberger, R. Bliss, R. A. Feldman, Brandon J. EssinkW. B. Smith, L. Chu, W. M. Seger, J. Saleh, J. L. Borders, M. Adams

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Abstract

Background The 2014 Zaire Ebola virus outbreak highlighted the need for a safe, effective vaccine with a rapid onset of protection. We report the safety and immunogenicity of the recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSV∆G-ZEBOV-GP) across a 6 log10 dose range in two sequential cohorts. Methods In this phase 1b double-blind, placebo-controlled, dose-response study we enrolled and randomly assigned healthy adults (aged 18–61 years) at eight study sites in the USA to receive a single injection of vaccine or placebo, administered by intramuscular injection. In cohort 1, participants were assigned to receive 3 × 103, 3 × 104, 3 × 105, or 3 × 106 PFU doses of rVSV∆G-ZEBOV-GP or placebo. In cohort 2, participants were assigned to receive 3 × 106, 9 × 106, 2 × 107, or 1 × 108 PFU doses of rVSV∆G-ZEBOV-GP or placebo. Participants were centrally allocated by the study statistician to vaccine groups or placebo through computer-generated randomisation lists. The primary safety outcome was incidence of adverse events within 14 days in the modified intention-to-treat population (all randomly assigned participants who received vaccine or placebo), and the primary outcome for immunogenicity was IgG ELISA antibody titres at day 28 in the per-protocol population. Surveillance was enhanced for arthritis and dermatitis through to day 56. This study is registered with ClinicalTrials.gov, number NCT02314923. Findings Between Dec 26, 2014, and June 8, 2015, 513 participants were enrolled and randomly assigned; one was not immunised because of unsuccessful phlebotomy. In cohort 1, 256 participants received vaccine (3 × 103 [n=64], 3 × 104 [n=64], 3 × 105 [n=64], or 3 × 106 PFU [n=64]) and 74 received placebo. In cohort 2, 162 participants received vaccine (3 × 106 [n=20], 9 × 106 [n=47], 2 × 107 [n=47], or 1 × 108 PFU [n=48]) and 20 received placebo. Most adverse events occurred in the first day after vaccination, and were mild to moderate in intensity, of a short duration, and more frequent at high vaccine doses (9 × 106 PFU and greater). At the 2 × 107 PFU dose (used in phase 3 trials), the most common local adverse events versus placebo within the first 14 days were arm pain (57·4% [27 of 47] vs 7·4% [seven of 94]) and local tenderness (59·6% [28 of 47] vs 8·5% [eight of 94]). The most common systemic adverse events at the 2 × 107 PFU dose versus placebo, occurring in the first 14 days, were headache (46·8% [22 of 47] vs 27·7% [26 of 94]), fatigue (38·3% [18 of 47] vs 19·1% [18 of 94]), myalgia (34·0% [16 of 47] vs 10·6% [10 of 94]), subjective fever (29·8% [14 of 47] vs 2·1% [two of 94]), shivering or chills (27·7% [13 of 47] vs 7·4% [seven of 94]), sweats (23·4% [11 of 47] vs 3·2% [three of 94]), joint aches and pain (19·1% [nine of 47] vs 7·4% [seven of 94]), objective fever (14·9% [seven of 47] vs 1·1% [one of 94]), and joint tenderness or swelling (14·9% [seven of 47] vs 2·1% [two of 94]). Self-limited, post-vaccination arthritis occurred in 4·5% (19 of 418) of vaccinees (median onset 12·0 days [IQR 10–14]; median duration 8·0 days [6–15]) versus 3·2% (three of 94) of controls (median onset 15·0 days [6–20]; median duration 47·0 days [37–339]), with no apparent dose relationship. Post-vaccination dermatitis occurred in 5·7% (24 of 418) of vaccinees (median onset 9·0 days [IQR 2–12]; median duration 7·0 days [4–9]) versus 3·2% (three of 94) of controls (median onset 5·0 days [3–53]; median duration 33·0 days [5–370]). A low-level, transient, dose-dependent viraemia occurred in concert with early reactogenicity. Antibody responses were observed in most participants by day 14. IgG and neutralising antibody titres were dose-related (p=0·0003 for IgG ELISA and p<0·0001 for the 60% plaque-reduction neutralisation test [PRNT60] by linear trend). On day 28 at the 2 × 107 PFU dose, the geometric mean IgG ELISA endpoint titre was 1624 (95% CI 1146–2302) and seroconversion was 95·7% (95% CI 85·5–98·8); the geometric mean neutralising antibody titre by PRNT60 was 250 (176–355) and seroconversion was 95·7% (85·5–98·8). These robust immunological responses were sustained for 1 year. Interpretation rVSV∆G-ZEBOV-GP was well tolerated and stimulated a rapid onset of binding and neutralising antibodies, which were maintained through to day 360. The immunogenicity results support selection of the 2 × 107 PFU dose. Funding Biomedical Advanced Research and Development Authority, US Department of Health and Human Services.

Original languageEnglish (US)
Pages (from-to)854-866
Number of pages13
JournalThe Lancet Infectious Diseases
Volume17
Issue number8
DOIs
StatePublished - Jan 1 2017

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Ebola Vaccines
Placebos
Safety
Vaccines
Immunoglobulin G
Neutralizing Antibodies
Ebolavirus
Vaccination
Enzyme-Linked Immunosorbent Assay
Dermatitis
Arthritis
Fever
United States Dept. of Health and Human Services
Shivering
Pain
Neutralization Tests
Chills
Vesicular Stomatitis
Phlebotomy
Sweat

All Science Journal Classification (ASJC) codes

  • Infectious Diseases

Cite this

Safety and immunogenicity of the rVSV∆G-ZEBOV-GP Ebola virus vaccine candidate in healthy adults : a phase 1b randomised, multicentre, double-blind, placebo-controlled, dose-response study. / Heppner, D. Gray; Kemp, Tracy L.; Martin, Brian K.; Ramsey, William J.; Nichols, Richard; Dasen, Emily J.; Link, Charles J.; Das, Rituparna; Xu, Zhi Jin; Sheldon, Eric A.; Nowak, Teresa A.; Monath, Thomas P.; Fusco, J.; Crowell, J.; Creager, J.; Klein, R.; Gerstenberger, E.; Bliss, R.; Feldman, R. A.; Essink, Brandon J.; Smith, W. B.; Chu, L.; Seger, W. M.; Saleh, J.; Borders, J. L.; Adams, M.

In: The Lancet Infectious Diseases, Vol. 17, No. 8, 01.01.2017, p. 854-866.

Research output: Contribution to journalArticle

Heppner, DG, Kemp, TL, Martin, BK, Ramsey, WJ, Nichols, R, Dasen, EJ, Link, CJ, Das, R, Xu, ZJ, Sheldon, EA, Nowak, TA, Monath, TP, Fusco, J, Crowell, J, Creager, J, Klein, R, Gerstenberger, E, Bliss, R, Feldman, RA, Essink, BJ, Smith, WB, Chu, L, Seger, WM, Saleh, J, Borders, JL & Adams, M 2017, 'Safety and immunogenicity of the rVSV∆G-ZEBOV-GP Ebola virus vaccine candidate in healthy adults: a phase 1b randomised, multicentre, double-blind, placebo-controlled, dose-response study', The Lancet Infectious Diseases, vol. 17, no. 8, pp. 854-866. https://doi.org/10.1016/S1473-3099(17)30313-4
Heppner, D. Gray ; Kemp, Tracy L. ; Martin, Brian K. ; Ramsey, William J. ; Nichols, Richard ; Dasen, Emily J. ; Link, Charles J. ; Das, Rituparna ; Xu, Zhi Jin ; Sheldon, Eric A. ; Nowak, Teresa A. ; Monath, Thomas P. ; Fusco, J. ; Crowell, J. ; Creager, J. ; Klein, R. ; Gerstenberger, E. ; Bliss, R. ; Feldman, R. A. ; Essink, Brandon J. ; Smith, W. B. ; Chu, L. ; Seger, W. M. ; Saleh, J. ; Borders, J. L. ; Adams, M. / Safety and immunogenicity of the rVSV∆G-ZEBOV-GP Ebola virus vaccine candidate in healthy adults : a phase 1b randomised, multicentre, double-blind, placebo-controlled, dose-response study. In: The Lancet Infectious Diseases. 2017 ; Vol. 17, No. 8. pp. 854-866.
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title = "Safety and immunogenicity of the rVSV∆G-ZEBOV-GP Ebola virus vaccine candidate in healthy adults: a phase 1b randomised, multicentre, double-blind, placebo-controlled, dose-response study",
abstract = "Background The 2014 Zaire Ebola virus outbreak highlighted the need for a safe, effective vaccine with a rapid onset of protection. We report the safety and immunogenicity of the recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSV∆G-ZEBOV-GP) across a 6 log10 dose range in two sequential cohorts. Methods In this phase 1b double-blind, placebo-controlled, dose-response study we enrolled and randomly assigned healthy adults (aged 18–61 years) at eight study sites in the USA to receive a single injection of vaccine or placebo, administered by intramuscular injection. In cohort 1, participants were assigned to receive 3 × 103, 3 × 104, 3 × 105, or 3 × 106 PFU doses of rVSV∆G-ZEBOV-GP or placebo. In cohort 2, participants were assigned to receive 3 × 106, 9 × 106, 2 × 107, or 1 × 108 PFU doses of rVSV∆G-ZEBOV-GP or placebo. Participants were centrally allocated by the study statistician to vaccine groups or placebo through computer-generated randomisation lists. The primary safety outcome was incidence of adverse events within 14 days in the modified intention-to-treat population (all randomly assigned participants who received vaccine or placebo), and the primary outcome for immunogenicity was IgG ELISA antibody titres at day 28 in the per-protocol population. Surveillance was enhanced for arthritis and dermatitis through to day 56. This study is registered with ClinicalTrials.gov, number NCT02314923. Findings Between Dec 26, 2014, and June 8, 2015, 513 participants were enrolled and randomly assigned; one was not immunised because of unsuccessful phlebotomy. In cohort 1, 256 participants received vaccine (3 × 103 [n=64], 3 × 104 [n=64], 3 × 105 [n=64], or 3 × 106 PFU [n=64]) and 74 received placebo. In cohort 2, 162 participants received vaccine (3 × 106 [n=20], 9 × 106 [n=47], 2 × 107 [n=47], or 1 × 108 PFU [n=48]) and 20 received placebo. Most adverse events occurred in the first day after vaccination, and were mild to moderate in intensity, of a short duration, and more frequent at high vaccine doses (9 × 106 PFU and greater). At the 2 × 107 PFU dose (used in phase 3 trials), the most common local adverse events versus placebo within the first 14 days were arm pain (57·4{\%} [27 of 47] vs 7·4{\%} [seven of 94]) and local tenderness (59·6{\%} [28 of 47] vs 8·5{\%} [eight of 94]). The most common systemic adverse events at the 2 × 107 PFU dose versus placebo, occurring in the first 14 days, were headache (46·8{\%} [22 of 47] vs 27·7{\%} [26 of 94]), fatigue (38·3{\%} [18 of 47] vs 19·1{\%} [18 of 94]), myalgia (34·0{\%} [16 of 47] vs 10·6{\%} [10 of 94]), subjective fever (29·8{\%} [14 of 47] vs 2·1{\%} [two of 94]), shivering or chills (27·7{\%} [13 of 47] vs 7·4{\%} [seven of 94]), sweats (23·4{\%} [11 of 47] vs 3·2{\%} [three of 94]), joint aches and pain (19·1{\%} [nine of 47] vs 7·4{\%} [seven of 94]), objective fever (14·9{\%} [seven of 47] vs 1·1{\%} [one of 94]), and joint tenderness or swelling (14·9{\%} [seven of 47] vs 2·1{\%} [two of 94]). Self-limited, post-vaccination arthritis occurred in 4·5{\%} (19 of 418) of vaccinees (median onset 12·0 days [IQR 10–14]; median duration 8·0 days [6–15]) versus 3·2{\%} (three of 94) of controls (median onset 15·0 days [6–20]; median duration 47·0 days [37–339]), with no apparent dose relationship. Post-vaccination dermatitis occurred in 5·7{\%} (24 of 418) of vaccinees (median onset 9·0 days [IQR 2–12]; median duration 7·0 days [4–9]) versus 3·2{\%} (three of 94) of controls (median onset 5·0 days [3–53]; median duration 33·0 days [5–370]). A low-level, transient, dose-dependent viraemia occurred in concert with early reactogenicity. Antibody responses were observed in most participants by day 14. IgG and neutralising antibody titres were dose-related (p=0·0003 for IgG ELISA and p<0·0001 for the 60{\%} plaque-reduction neutralisation test [PRNT60] by linear trend). On day 28 at the 2 × 107 PFU dose, the geometric mean IgG ELISA endpoint titre was 1624 (95{\%} CI 1146–2302) and seroconversion was 95·7{\%} (95{\%} CI 85·5–98·8); the geometric mean neutralising antibody titre by PRNT60 was 250 (176–355) and seroconversion was 95·7{\%} (85·5–98·8). These robust immunological responses were sustained for 1 year. Interpretation rVSV∆G-ZEBOV-GP was well tolerated and stimulated a rapid onset of binding and neutralising antibodies, which were maintained through to day 360. The immunogenicity results support selection of the 2 × 107 PFU dose. Funding Biomedical Advanced Research and Development Authority, US Department of Health and Human Services.",
author = "Heppner, {D. Gray} and Kemp, {Tracy L.} and Martin, {Brian K.} and Ramsey, {William J.} and Richard Nichols and Dasen, {Emily J.} and Link, {Charles J.} and Rituparna Das and Xu, {Zhi Jin} and Sheldon, {Eric A.} and Nowak, {Teresa A.} and Monath, {Thomas P.} and J. Fusco and J. Crowell and J. Creager and R. Klein and E. Gerstenberger and R. Bliss and Feldman, {R. A.} and Essink, {Brandon J.} and Smith, {W. B.} and L. Chu and Seger, {W. M.} and J. Saleh and Borders, {J. L.} and M. Adams",
year = "2017",
month = "1",
day = "1",
doi = "10.1016/S1473-3099(17)30313-4",
language = "English (US)",
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pages = "854--866",
journal = "The Lancet Infectious Diseases",
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TY - JOUR

T1 - Safety and immunogenicity of the rVSV∆G-ZEBOV-GP Ebola virus vaccine candidate in healthy adults

T2 - a phase 1b randomised, multicentre, double-blind, placebo-controlled, dose-response study

AU - Heppner, D. Gray

AU - Kemp, Tracy L.

AU - Martin, Brian K.

AU - Ramsey, William J.

AU - Nichols, Richard

AU - Dasen, Emily J.

AU - Link, Charles J.

AU - Das, Rituparna

AU - Xu, Zhi Jin

AU - Sheldon, Eric A.

AU - Nowak, Teresa A.

AU - Monath, Thomas P.

AU - Fusco, J.

AU - Crowell, J.

AU - Creager, J.

AU - Klein, R.

AU - Gerstenberger, E.

AU - Bliss, R.

AU - Feldman, R. A.

AU - Essink, Brandon J.

AU - Smith, W. B.

AU - Chu, L.

AU - Seger, W. M.

AU - Saleh, J.

AU - Borders, J. L.

AU - Adams, M.

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Background The 2014 Zaire Ebola virus outbreak highlighted the need for a safe, effective vaccine with a rapid onset of protection. We report the safety and immunogenicity of the recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSV∆G-ZEBOV-GP) across a 6 log10 dose range in two sequential cohorts. Methods In this phase 1b double-blind, placebo-controlled, dose-response study we enrolled and randomly assigned healthy adults (aged 18–61 years) at eight study sites in the USA to receive a single injection of vaccine or placebo, administered by intramuscular injection. In cohort 1, participants were assigned to receive 3 × 103, 3 × 104, 3 × 105, or 3 × 106 PFU doses of rVSV∆G-ZEBOV-GP or placebo. In cohort 2, participants were assigned to receive 3 × 106, 9 × 106, 2 × 107, or 1 × 108 PFU doses of rVSV∆G-ZEBOV-GP or placebo. Participants were centrally allocated by the study statistician to vaccine groups or placebo through computer-generated randomisation lists. The primary safety outcome was incidence of adverse events within 14 days in the modified intention-to-treat population (all randomly assigned participants who received vaccine or placebo), and the primary outcome for immunogenicity was IgG ELISA antibody titres at day 28 in the per-protocol population. Surveillance was enhanced for arthritis and dermatitis through to day 56. This study is registered with ClinicalTrials.gov, number NCT02314923. Findings Between Dec 26, 2014, and June 8, 2015, 513 participants were enrolled and randomly assigned; one was not immunised because of unsuccessful phlebotomy. In cohort 1, 256 participants received vaccine (3 × 103 [n=64], 3 × 104 [n=64], 3 × 105 [n=64], or 3 × 106 PFU [n=64]) and 74 received placebo. In cohort 2, 162 participants received vaccine (3 × 106 [n=20], 9 × 106 [n=47], 2 × 107 [n=47], or 1 × 108 PFU [n=48]) and 20 received placebo. Most adverse events occurred in the first day after vaccination, and were mild to moderate in intensity, of a short duration, and more frequent at high vaccine doses (9 × 106 PFU and greater). At the 2 × 107 PFU dose (used in phase 3 trials), the most common local adverse events versus placebo within the first 14 days were arm pain (57·4% [27 of 47] vs 7·4% [seven of 94]) and local tenderness (59·6% [28 of 47] vs 8·5% [eight of 94]). The most common systemic adverse events at the 2 × 107 PFU dose versus placebo, occurring in the first 14 days, were headache (46·8% [22 of 47] vs 27·7% [26 of 94]), fatigue (38·3% [18 of 47] vs 19·1% [18 of 94]), myalgia (34·0% [16 of 47] vs 10·6% [10 of 94]), subjective fever (29·8% [14 of 47] vs 2·1% [two of 94]), shivering or chills (27·7% [13 of 47] vs 7·4% [seven of 94]), sweats (23·4% [11 of 47] vs 3·2% [three of 94]), joint aches and pain (19·1% [nine of 47] vs 7·4% [seven of 94]), objective fever (14·9% [seven of 47] vs 1·1% [one of 94]), and joint tenderness or swelling (14·9% [seven of 47] vs 2·1% [two of 94]). Self-limited, post-vaccination arthritis occurred in 4·5% (19 of 418) of vaccinees (median onset 12·0 days [IQR 10–14]; median duration 8·0 days [6–15]) versus 3·2% (three of 94) of controls (median onset 15·0 days [6–20]; median duration 47·0 days [37–339]), with no apparent dose relationship. Post-vaccination dermatitis occurred in 5·7% (24 of 418) of vaccinees (median onset 9·0 days [IQR 2–12]; median duration 7·0 days [4–9]) versus 3·2% (three of 94) of controls (median onset 5·0 days [3–53]; median duration 33·0 days [5–370]). A low-level, transient, dose-dependent viraemia occurred in concert with early reactogenicity. Antibody responses were observed in most participants by day 14. IgG and neutralising antibody titres were dose-related (p=0·0003 for IgG ELISA and p<0·0001 for the 60% plaque-reduction neutralisation test [PRNT60] by linear trend). On day 28 at the 2 × 107 PFU dose, the geometric mean IgG ELISA endpoint titre was 1624 (95% CI 1146–2302) and seroconversion was 95·7% (95% CI 85·5–98·8); the geometric mean neutralising antibody titre by PRNT60 was 250 (176–355) and seroconversion was 95·7% (85·5–98·8). These robust immunological responses were sustained for 1 year. Interpretation rVSV∆G-ZEBOV-GP was well tolerated and stimulated a rapid onset of binding and neutralising antibodies, which were maintained through to day 360. The immunogenicity results support selection of the 2 × 107 PFU dose. Funding Biomedical Advanced Research and Development Authority, US Department of Health and Human Services.

AB - Background The 2014 Zaire Ebola virus outbreak highlighted the need for a safe, effective vaccine with a rapid onset of protection. We report the safety and immunogenicity of the recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSV∆G-ZEBOV-GP) across a 6 log10 dose range in two sequential cohorts. Methods In this phase 1b double-blind, placebo-controlled, dose-response study we enrolled and randomly assigned healthy adults (aged 18–61 years) at eight study sites in the USA to receive a single injection of vaccine or placebo, administered by intramuscular injection. In cohort 1, participants were assigned to receive 3 × 103, 3 × 104, 3 × 105, or 3 × 106 PFU doses of rVSV∆G-ZEBOV-GP or placebo. In cohort 2, participants were assigned to receive 3 × 106, 9 × 106, 2 × 107, or 1 × 108 PFU doses of rVSV∆G-ZEBOV-GP or placebo. Participants were centrally allocated by the study statistician to vaccine groups or placebo through computer-generated randomisation lists. The primary safety outcome was incidence of adverse events within 14 days in the modified intention-to-treat population (all randomly assigned participants who received vaccine or placebo), and the primary outcome for immunogenicity was IgG ELISA antibody titres at day 28 in the per-protocol population. Surveillance was enhanced for arthritis and dermatitis through to day 56. This study is registered with ClinicalTrials.gov, number NCT02314923. Findings Between Dec 26, 2014, and June 8, 2015, 513 participants were enrolled and randomly assigned; one was not immunised because of unsuccessful phlebotomy. In cohort 1, 256 participants received vaccine (3 × 103 [n=64], 3 × 104 [n=64], 3 × 105 [n=64], or 3 × 106 PFU [n=64]) and 74 received placebo. In cohort 2, 162 participants received vaccine (3 × 106 [n=20], 9 × 106 [n=47], 2 × 107 [n=47], or 1 × 108 PFU [n=48]) and 20 received placebo. Most adverse events occurred in the first day after vaccination, and were mild to moderate in intensity, of a short duration, and more frequent at high vaccine doses (9 × 106 PFU and greater). At the 2 × 107 PFU dose (used in phase 3 trials), the most common local adverse events versus placebo within the first 14 days were arm pain (57·4% [27 of 47] vs 7·4% [seven of 94]) and local tenderness (59·6% [28 of 47] vs 8·5% [eight of 94]). The most common systemic adverse events at the 2 × 107 PFU dose versus placebo, occurring in the first 14 days, were headache (46·8% [22 of 47] vs 27·7% [26 of 94]), fatigue (38·3% [18 of 47] vs 19·1% [18 of 94]), myalgia (34·0% [16 of 47] vs 10·6% [10 of 94]), subjective fever (29·8% [14 of 47] vs 2·1% [two of 94]), shivering or chills (27·7% [13 of 47] vs 7·4% [seven of 94]), sweats (23·4% [11 of 47] vs 3·2% [three of 94]), joint aches and pain (19·1% [nine of 47] vs 7·4% [seven of 94]), objective fever (14·9% [seven of 47] vs 1·1% [one of 94]), and joint tenderness or swelling (14·9% [seven of 47] vs 2·1% [two of 94]). Self-limited, post-vaccination arthritis occurred in 4·5% (19 of 418) of vaccinees (median onset 12·0 days [IQR 10–14]; median duration 8·0 days [6–15]) versus 3·2% (three of 94) of controls (median onset 15·0 days [6–20]; median duration 47·0 days [37–339]), with no apparent dose relationship. Post-vaccination dermatitis occurred in 5·7% (24 of 418) of vaccinees (median onset 9·0 days [IQR 2–12]; median duration 7·0 days [4–9]) versus 3·2% (three of 94) of controls (median onset 5·0 days [3–53]; median duration 33·0 days [5–370]). A low-level, transient, dose-dependent viraemia occurred in concert with early reactogenicity. Antibody responses were observed in most participants by day 14. IgG and neutralising antibody titres were dose-related (p=0·0003 for IgG ELISA and p<0·0001 for the 60% plaque-reduction neutralisation test [PRNT60] by linear trend). On day 28 at the 2 × 107 PFU dose, the geometric mean IgG ELISA endpoint titre was 1624 (95% CI 1146–2302) and seroconversion was 95·7% (95% CI 85·5–98·8); the geometric mean neutralising antibody titre by PRNT60 was 250 (176–355) and seroconversion was 95·7% (85·5–98·8). These robust immunological responses were sustained for 1 year. Interpretation rVSV∆G-ZEBOV-GP was well tolerated and stimulated a rapid onset of binding and neutralising antibodies, which were maintained through to day 360. The immunogenicity results support selection of the 2 × 107 PFU dose. Funding Biomedical Advanced Research and Development Authority, US Department of Health and Human Services.

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U2 - 10.1016/S1473-3099(17)30313-4

DO - 10.1016/S1473-3099(17)30313-4

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VL - 17

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JO - The Lancet Infectious Diseases

JF - The Lancet Infectious Diseases

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