Safety, tolerability, and immunogenicity of the chimpanzee adenovirus type 3-vectored Marburg virus (cAd3-Marburg) vaccine in healthy adults in the USA: a first-in-human, phase 1, open-label, dose-escalation trial.

Animals Adult Humans Pan troglodytes Marburgvirus Antibodies, Viral Adenoviruses, Simian Vaccines, Synthetic / adverse effects Adenoviridae Glycoproteins Double-Blind Method

Journal

Lancet (London, England)
ISSN: 1474-547X
Titre abrégé: Lancet
Pays: England
ID NLM: 2985213R

Informations de publication

Date de publication:
28 01 2023
Historique:
received: 02 09 2022
revised: 14 10 2022
accepted: 15 11 2022
pmc-release: 28 01 2024
entrez: 28 1 2023
pubmed: 29 1 2023
medline: 1 2 2023
Statut: ppublish

Résumé

WHO has identified Marburg virus as an emerging virus requiring urgent vaccine research and development, particularly due to its recent emergence in Ghana. We report results from a first-in-human clinical trial evaluating a replication-deficient recombinant chimpanzee adenovirus type 3 (cAd3)-vectored vaccine encoding a wild-type Marburg virus Angola glycoprotein (cAd3-Marburg) in healthy adults. We did a first-in-human, phase 1, open-label, dose-escalation trial of the cAd3-Marburg vaccine at the Walter Reed Army Institute of Research Clinical Trials Center in the USA. Healthy adults aged 18-50 years were assigned to receive a single intramuscular dose of cAd3-Marburg vaccine at either 1 × 10 Between Oct 9, 2018, and Jan 31, 2019, 40 healthy adults were enrolled and assigned to receive a single intramuscular dose of cAd3-Marburg vaccine at either 1 × 10 This first-in-human trial of this cAd3-Marburg vaccine showed the agent is safe and immunogenic, with a safety profile similar to previously tested cAd3-vectored filovirus vaccines. 95% of participants produced a glycoprotein-specific antibody response at 4 weeks after a single vaccination, which remained in 70% of participants at 48 weeks. These findings represent a crucial step in the development of a vaccine for emergency deployment against a re-emerging pathogen that has recently expanded its reach to new regions. National Institutes of Health.

Sections du résumé

BACKGROUND
WHO has identified Marburg virus as an emerging virus requiring urgent vaccine research and development, particularly due to its recent emergence in Ghana. We report results from a first-in-human clinical trial evaluating a replication-deficient recombinant chimpanzee adenovirus type 3 (cAd3)-vectored vaccine encoding a wild-type Marburg virus Angola glycoprotein (cAd3-Marburg) in healthy adults.
METHODS
We did a first-in-human, phase 1, open-label, dose-escalation trial of the cAd3-Marburg vaccine at the Walter Reed Army Institute of Research Clinical Trials Center in the USA. Healthy adults aged 18-50 years were assigned to receive a single intramuscular dose of cAd3-Marburg vaccine at either 1 × 10
FINDINGS
Between Oct 9, 2018, and Jan 31, 2019, 40 healthy adults were enrolled and assigned to receive a single intramuscular dose of cAd3-Marburg vaccine at either 1 × 10
INTERPRETATION
This first-in-human trial of this cAd3-Marburg vaccine showed the agent is safe and immunogenic, with a safety profile similar to previously tested cAd3-vectored filovirus vaccines. 95% of participants produced a glycoprotein-specific antibody response at 4 weeks after a single vaccination, which remained in 70% of participants at 48 weeks. These findings represent a crucial step in the development of a vaccine for emergency deployment against a re-emerging pathogen that has recently expanded its reach to new regions.
FUNDING
National Institutes of Health.

Identifiants

DOI: 10.1016/S0140-6736(22)02400-X PMID: 36709074 PMC: PMC10127441
pubmed: 36709074
pii: S0140-6736(22)02400-X
doi: 10.1016/S0140-6736(22)02400-X
pmc: PMC10127441
mid: NIHMS1871339
pii:
doi:

Substances chimiques

Antibodies, Viral 0
Vaccines, Synthetic 0
Glycoproteins 0

Banques de données

ClinicalTrials.gov
['NCT03475056']

Types de publication

Clinical Trial, Phase I Journal Article Research Support, N.I.H., Extramural

Langues

eng

Sous-ensembles de citation

IM

Pagination

294-302

Subventions

Organisme : Intramural NIH HHS
ID : Z99 AI999999
Pays : United States

Investigateurs

Rebecca Lampley (R)
Brenda Larkin (B)
Pamela Costner (P)
Hope Wilson (H)
Mike Read (M)

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2020 Elsevier Ltd. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests NJS is listed on patents involving cAd3-vectored vaccines. All other authors declare no competing interests.

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Auteurs

Melinda J Hamer (MJ)

Walter Reed Army Institute of Research, Silver Spring, MD, USA; Department of Emergency Medicine, George Washington University School of Medicine and Health Sciences, Washington, DC, USA.

Katherine V Houser (KV)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA. Electronic address: katherine.houser@nih.gov.

Amelia R Hofstetter (AR)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Ana M Ortega-Villa (AM)

Biostatistics Research Branch, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Christine Lee (C)

Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Anne Preston (A)

Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Brooke Augustine (B)

Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Charla Andrews (C)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Galina V Yamshchikov (GV)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Somia Hickman (S)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Steven Schech (S)

Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Jack N Hutter (JN)

Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Paul T Scott (PT)

Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Paige E Waterman (PE)

Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Mihret F Amare (MF)

Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Victoria Kioko (V)

Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Casey Storme (C)

Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Kayvon Modjarrad (K)

Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Melanie D McCauley (MD)

Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Merlin L Robb (ML)

Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.

Martin R Gaudinski (MR)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Ingelise J Gordon (IJ)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

LaSonji A Holman (LA)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Alicia T Widge (AT)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Larisa Strom (L)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Myra Happe (M)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Josephine H Cox (JH)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Sandra Vazquez (S)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Daphne A Stanley (DA)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Tamar Murray (T)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Caitlyn N M Dulan (CNM)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Ruth Hunegnaw (R)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Sandeep R Narpala (SR)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Phillip A Swanson (PA)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Manjula Basappa (M)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Jagada Thillainathan (J)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Marcelino Padilla (M)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Britta Flach (B)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Sarah O'Connell (S)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Olga Trofymenko (O)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Patricia Morgan (P)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Emily E Coates (EE)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Jason G Gall (JG)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Adrian B McDermott (AB)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Richard A Koup (RA)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

John R Mascola (JR)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Aurélie Ploquin (A)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Nancy J Sullivan (NJ)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

Julie A Ake (JA)

Walter Reed Army Institute of Research, Silver Spring, MD, USA.

Julie E Ledgerwood (JE)

Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Safety, tolerability, and immunogenicity of...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Safety, tolerability, and immunogenicity of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Safety, tolerability, and immunogenicity of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Pan troglodytes › Safety, tolerability, and immunogenicity of...
questionsmedicales.fr › Virus › Virus à ARN › Virus à ARN de polarité négative › Mononegavirales › Filoviridae › Marburgvirus › Safety, tolerability, and immunogenicity of...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Globulines › Sérum-globulines › Immunoglobulines › Anticorps › Anticorps antiviraux › Safety, tolerability, and immunogenicity of...
questionsmedicales.fr › Virus › Virus à ADN › Adenoviridae › Mastadenovirus › Adénovirus simiens › Safety, tolerability, and immunogenicity of...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Vaccins synthétiques › Safety, tolerability, and immunogenicity of...
questionsmedicales.fr › Virus › Virus à ADN › Adenoviridae › Safety, tolerability, and immunogenicity of...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Glycoprotéines › Safety, tolerability, and immunogenicity of...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Méthodologie en recherche épidémiologique › Méthode en double aveugle › Safety, tolerability, and immunogenicity of...