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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

Title: 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
Authors: Hamer, Melinda J; Houser, Katherine; Hofstetter, Amelia R; Ortega-Villa, Ana M; Lee, Christine; Preston, Anne; Augustine, Brooke; Andrews, Charla; Yamshchikov, Galina; Hickman, Somia; Schech, Steven; Hutter, Jack N; Scott, Paul T; Waterman, Paige E; Amare, Mihret F; Kioko, Victoria; Storme, Casey; Modjarrad, Kayvon; McCauley, Melanie D; Robb, Merlin L; Gaudinski, Martin R; Gordon, Ingelise J; Holman, LaSonji A; Widge, Alicia T; Strom, Larisa; Happe, Myra; Cox, Josephine H; Vazquez, Sandra; Stanley, Daphne A; Murray, Tamar; Dulan, Caitlyn NM; Hunegnaw, Ruth; Narpala, Sandeep R; Swanson II, Phillip A; Basappa, Manjula; Thillainathan, Jagada; Padilla, Marcelino; Flach, Britta; O'Connell, Sarah; Trofymenko, Olga; Morgan, Patricia; Coates, Emily E; Gall, Jason G; McDermott, Adrian B; Koup, Richard A; Mascola, John R; Ploquin, Aurelie; Sullivan, Nancy J; Ake, Julie A; Ledgerwood, Julie E; RV 507 Study Team
Source: The Lancet , 401 (10373) pp. 294-302. (2023)
Publisher Information: Elsevier
Publication Year: 2023
Collection: University College London: UCL Discovery
Description: 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 × 1010 or 1 × 1011 particle units (pu). Primary safety endpoints included reactogenicity assessed for the first 7 days and all adverse events assessed for 28 days after vaccination. Secondary immunogenicity endpoints were assessment of binding antibody responses and T-cell responses against the Marburg virus glycoprotein insert, and assessment of neutralising antibody responses against the cAd3 vector 4 weeks after vaccination. This study is registered with ClinicalTrials.gov, NCT03475056. // 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 × 1010 pu (n=20) or 1 × 1011 pu (n=20). The cAd3-Marburg vaccine was safe, well tolerated, and immunogenic. All enrolled participants received cAd3-Marburg vaccine, with 37 (93%) participants completing follow-up visits; two (5%) participants moved from the area and one (3%) was lost to follow-up. No serious adverse events related to vaccination occurred. Mild to moderate reactogenicity was observed after vaccination, with symptoms of injection site pain and tenderness (27 [68%] of 40 participants), malaise (18 [45%] of 40 participants), headache (17 [43%] of 40 participants), and myalgia (14 [35%] of 40 participants) most commonly reported. ...
Document Type: article in journal/newspaper
File Description: text
Language: English
Relation: https://discovery.ucl.ac.uk/id/eprint/10217962/
Availability: https://discovery.ucl.ac.uk/id/eprint/10217962/1/nihms-1871339.pdf; https://discovery.ucl.ac.uk/id/eprint/10217962/
Rights: open
Accession Number: edsbas.427FA8C
Database: BASE