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JAMA. 2016 Apr 19;315(15):1610-23. doi: 10.1001/jama.2016.4218.

Safety and Immunogenicity of Novel Adenovirus Type 26- and Modified Vaccinia Ankara-Vectored Ebola Vaccines: A Randomized Clinical Trial.

Author information

1
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, United Kingdom.
2
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, United Kingdom2Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, United Kingdom.
3
Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.
4
Janssen, Pharmaceutical Companies of Johnson & Johnson, Leiden, the Netherlands.
5
Bavarian Nordic, Martinsried, Germany.
6
Jenner Institute, Centre for Clinical Vaccinology and Tropical Medicine, University of Oxford, Oxford, United Kingdom7National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, Oxford, United Kingdom.
7
Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom.
8
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, United Kingdom7National Institute for Health Research (NIHR) Oxford Biomedical Research Centre, Oxford, United Kingdom.

Abstract

IMPORTANCE:

Developing effective vaccines against Ebola virus is a global priority.

OBJECTIVE:

To evaluate an adenovirus type 26 vector vaccine encoding Ebola glycoprotein (Ad26.ZEBOV) and a modified vaccinia Ankara vector vaccine, encoding glycoproteins from Ebola virus, Sudan virus, Marburg virus, and Tai Forest virus nucleoprotein (MVA-BN-Filo).

DESIGN, SETTING, AND PARTICIPANTS:

Single-center, randomized, placebo-controlled, observer-blind, phase 1 trial performed in Oxford, United Kingdom, enrolling healthy 18- to 50-year-olds from December 2014; 8-month follow-up was completed October 2015.

INTERVENTIONS:

Participants were randomized into 4 groups, within which they were simultaneously randomized 5:1 to receive study vaccines or placebo. Those receiving active vaccines were primed with Ad26.ZEBOV (5 × 10(10) viral particles) or MVA-BN-Filo (1 × 10(8) median tissue culture infective dose) and boosted with the alternative vaccine 28 or 56 days later. A fifth, open-label group received Ad26.ZEBOV boosted by MVA-BN-Filo 14 days later.

MAIN OUTCOMES AND MEASURES:

The primary outcomes were safety and tolerability. All adverse events were recorded until 21 days after each immunization; serious adverse events were recorded throughout the trial. Secondary outcomes were humoral and cellular immune responses to immunization, as assessed by enzyme-linked immunosorbent assay and enzyme-linked immunospot performed at baseline and from 7 days after each immunization until 8 months after priming immunizations.

RESULTS:

Among 87 study participants (median age, 38.5 years; 66.7% female), 72 were randomized into 4 groups of 18, and 15 were included in the open-label group. Four participants did not receive a booster dose; 67 of 75 study vaccine recipients were followed up at 8 months. No vaccine-related serious adverse events occurred. No participant became febrile after MVA-BN-Filo, compared with 3 of 60 participants (5%; 95% CI, 1%-14%) receiving Ad26.ZEBOV in the randomized groups. In the open-label group, 4 of 15 Ad26.ZEBOV recipients (27%; 95% CI, 8%-55%) experienced fever. In the randomized groups, 28 of 29 Ad26.ZEBOV recipients (97%; 95% CI, 82%- 99.9%) and 7 of 30 MVA-BN-Filo recipients (23%; 95% CI, 10%-42%) had detectable Ebola glycoprotein-specific IgG 28 days after primary immunization. All vaccine recipients had specific IgG detectable 21 days postboost and at 8-month follow-up. Within randomized groups, at 7 days postboost, at least 86% of vaccine recipients showed Ebola-specific T-cell responses.

CONCLUSIONS AND RELEVANCE:

In this phase 1 study of healthy volunteers, immunization with Ad26.ZEBOV or MVA-BN-Filo did not result in any vaccine-related serious adverse events. An immune response was observed after primary immunization with Ad26.ZEBOV; boosting by MVA-BN-Filo resulted in sustained elevation of specific immunity. These vaccines are being further assessed in phase 2 and 3 studies.

TRIAL REGISTRATION:

clinicaltrials.gov Identifier: NCT02313077.

PMID:
27092831
DOI:
10.1001/jama.2016.4218
[Indexed for MEDLINE]

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