Evidence map›Paper›PMID 39374605›Full record

Trial reportThe Lancet. Microbe2024

Safety and immunogenicity of a delayed booster dose of the rVSVΔG-ZEBOV-GP vaccine for prevention of Ebola virus disease: a multicentre, open-label, phase 2 randomised controlled trial.

Richard T Davey, Gary L Collins, Nadine Rouphael, Guillaume Poliquin, Rosemary McConnell, Gabrielle Grubbs, Susan L Moir, Joanne M Langley, Marc Teitelbaum, Angela L Hewlett and 16 more

Registry-linked trialAbstract readClinical Trial, Phase IIRandomized Controlled TrialMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The Lancet. Microbe, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02788227 (A Multicenter Study of the Immunogenicity of Recombinant Vesicular Stomatitis Vaccine for Ebola-Zaire), which is not on this map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT02788227 phase2completednot on this map

A Multicenter Study of the Immunogenicity of Recombinant Vesicular Stomatitis Vaccine for Ebola-Zaire (rVSV∆G-ZEBOV-GP Vaccine) for Pre-Exposure Prophylaxis in Individuals at Potential Occupational Risk for Ebola Virus Exposure (PREPARE)

TypeinterventionalSponsorNational Institutes of Health Clinical Center (CC)Ran2016 to 2025Enrolled248ConditionsHealthy VolunteersArmsrVSV∆G-ZEBOV-GP Vaccine (V920)
3 · Its place in the literature

Who cites it

6 citing papers in PubMed.

  1. Trial
  2. Article
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  5. Article
  6. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

26 authors.

Richard T DaveyNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address: rdavey@niaid.nih.gov.
Gary L CollinsDivision of Biostatistics, University of Minnesota, Minneapolis, MN, USA.
Nadine RouphaelHope Clinic of Emory Vaccine Center, Emory University, Atlanta, GA, USA.
Guillaume PoliquinPublic Health Agency of Canada, Children's Hospital Research Institute, Winnipeg, MB, Canada.
Rosemary McConnellCritical Care Medicine Department, Clinical Research Center, National Institutes of Health, Bethesda, MD, USA.
Gabrielle GrubbsDivision of Viral Products, Center for Biologics Evaluation and Research, US Food & Drug Administration, Silver Spring, MD, USA.
Susan L MoirNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Joanne M LangleyCanadian Center for Vaccinology, IWK Health Centre and Nova Scotia Health Authority, Dalhousie University, Halifax, NS, Canada.
Marc TeitelbaumClinical Monitoring Research Program, Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Angela L HewlettDivision of Infectious Diseases, University of Nebraska Medical Center, Omaha, NE, USA.
Susan L F McLellanDivision of Infectious Diseases, Dept of Medicine, School of Medicine, University of Texas Medical Branch, Galveston, TX, USA.
Nahid BhadeliaBoston University Center for Emerging Infectious Diseases Policy and Research, Boston University, Boston, MA, USA.
Vanessa N RaabeNew York University Grossman School of Medicine, New York, NY, USA.
Mark J MulliganNew York University Grossman School of Medicine, New York, NY, USA.
Irina Maljkovic BerryIntegrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA.
Bonnie Dighero-KempIntegrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA.
Jonathan R KurtzIntegrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA.
Lisa E HensleyIntegrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA.
Nelson C E DozierIntegrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA.
Lindsay C B MarronIntegrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA.
Alain DuCheneDivision of Biostatistics, University of Minnesota, Minneapolis, MN, USA.
Jens H KuhnIntegrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, Frederick, MD, USA.
Shawn K BrownApplied and Developmental Research Directorate, Frederick National Laboratory for Cancer Research, Frederick, MD, USA.
Surender KhuranaDivision of Viral Products, Center for Biologics Evaluation and Research, US Food & Drug Administration, Silver Spring, MD, USA.
H Clifford LaneNational Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
James D NeatonDivision of Biostatistics, University of Minnesota, Minneapolis, MN, USA.

Funding

Influenza and Emerging Infectious DiseasesZ01AI000984 · NIAID · NIAID EXTRAMURAL ACTIVITIES · PI DAVEY, RICHARD · 2007 to 2008
$2.0M
Intramural NIH HHS Z01 AI000984NIH HHS HHSN272200700016INIH HHS HHSN272201800013C
6 · The paper itself

Abstract

backgroundrVSVΔG-ZEBOV-GP is the first approved vaccine with clinical efficacy against Ebola virus disease. Although a seroprotective threshold has not been defined for those at occupational risk of exposure, the current vaccine strategy is to attain a sustained high level of antibody titres. The aim of this trial was to explore the effects of delayed boosting upon both the height and duration of antibody titres following primary immunisation.

methodsIn this open-label phase 2 randomised controlled trial, we compared antibody titres at month 36 in participants who had received a homologous booster dose at month 18 following primary immunisation with those who had received no booster. From Oct 25, 2016, to Jan 29, 2020, healthy adults aged 18 years or older deemed at occupational risk of exposure to Ebola virus due to laboratory work, clinical duties, or travel to an active endemic region were recruited from four hospital clinics in the USA and one hospital clinic in Canada and received primary vaccination with 2×10

findingsOf the 248 participants who enrolled and received their primary immunisation, 114 proceeded to the randomisation step at month 18. The two randomisation groups were balanced: 57 participants (24 [42%] of whom were female; median age was 42 years [IQR 35-50]) were randomly assigned to the booster group and 57 (24 [42%] of whom were female; median age was 42 years [IQR 36-51]) to the no-booster group. Of those randomly assigned, 92 participants (45 in the booster group and 47 in the no-booster group) completed 36 months of follow-up. At 18 months after primary immunisation, GMTs in the no-booster group increased from a baseline of 10 ELISA units (EU)/mL (95% CI 7-14) to 1451 EU/mL (1118-1882); GMTs in the booster group increased from 9 EU/mL (6-16) to 1769 EU/mL (1348-2321). At month 19, GMTs were 31 408 EU/mL (23 181-42 554) for the booster group and 1406 EU/mL (1078-1833) for the no-booster group; at month 36, GMTs were 10 146 EU/mL (7960-12 933) for the booster group and 1240 EU/mL (984-1563) for the no-booster group. Accordingly, the geometric mean ratio (GMR) of antibody titres had increased almost 21-fold more in the booster versus no-booster group at 1 month after booster administration (GMR 20·6; 95% CI 18·2-23·0; p<0·0001) and was still over 7-fold higher at month 36 (GMR 7·8; 95% CI 5·5-10·2; p<0·0001). Consistent with previous reports of this vaccine's side-effects, transient mono-articular or oligo-articular arthritis was diagnosed in 18 (9%) of 207 primary vaccination recipients; after randomisation, arthritis was diagnosed in one (2%) of 57 participants in the no-booster group. No new cases of arthritis developed after booster administration. Four serious adverse events occurred following randomisation: one (epistaxis) in the booster group and three (gastrointestinal haemorrhage, prostate cancer, and tachyarrhythmia) in the no-booster group. None of the serious adverse events was judged attributable to the booster vaccination assignment.

interpretationIn addition to no new safety concerns and in marked contrast to earlier trials evaluating short-term boosting, delaying a rVSVΔG-ZEBOV-GP booster until month 18 resulted in an increase in GMT that remained several-fold above the no-booster group GMT for at least 18 months. These findings could have implications for defining the optimal timing of booster doses as pre-exposure prophylaxis in populations at ongoing risk for Ebola virus exposure.

fundingThe Division of Intramural Research and the Division of Clinical Research of the National Institute of Allergy and Infectious Diseases at the US National Institutes of Health, Canadian Immunization Research Network through the Public Health Agency of Canada, Canadian Institutes of Health Research, and the US Defense Threat Reduction Agency.

Indexed as

Antibodies, ViralEbola VaccinesEbolavirusHemorrhagic Fever, EbolaImmunization, SecondaryAdultCanadaFemaleHumansImmunogenicity, VaccineMaleMiddle AgedUnited StatesYoung AdultAntibodies, ViralEbola Vaccines

Identifiers

PMID39374605
PMCPMC11560587

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Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.