• Melinda J Hamer, Katherine V Houser, Amelia R Hofstetter, Ana M Ortega-Villa, Christine Lee, Anne Preston, Brooke Augustine, Charla Andrews, Galina V Yamshchikov, Somia Hickman, Steven Schech, Jack N Hutter, Paul T Scott, Paige E Waterman, Mihret F Amare, Victoria Kioko, Casey Storme, Kayvon Modjarrad, Melanie D McCauley, Merlin L Robb, Martin R Gaudinski, Ingelise J Gordon, LaSonji A Holman, Alicia T Widge, Larisa Strom, Myra Happe, Josephine H Cox, Sandra Vazquez, Daphne A Stanley, Tamar Murray, Caitlyn N M Dulan, Ruth Hunegnaw, Sandeep R Narpala, Phillip A Swanson, Manjula Basappa, Jagada Thillainathan, Marcelino Padilla, Britta Flach, Sarah O'Connell, Olga Trofymenko, Patricia Morgan, Emily E Coates, Jason G Gall, Adrian B McDermott, Richard A Koup, John R Mascola, Aurélie Ploquin, Nancy J Sullivan, Julie A Ake, Julie E Ledgerwood, and RV 507 Study Team.
• 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.
• Lancet. 2023 Jan 28; 401 (10373): 294302294-302.

BackgroundWHO 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.MethodsWe 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.FindingsBetween 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. Glycoprotein-specific antibodies were induced in 38 (95%) of 40 participants 4 weeks after vaccination, with geometric mean titres of 421 [95% CI 209-846] in the 1 × 1010 pu group and 545 [276-1078] in the 1 × 1011 pu group, and remained significantly elevated at 48 weeks compared with baseline titres (39 [95% CI 13-119] in the 1 ×1010 pu group and 27 [95-156] in the 1 ×1011 pu group; both p<0·0001). T-cell responses to the glycoprotein insert and neutralising responses against the cAd3 vector were also increased at 4 weeks after vaccination.InterpretationThis 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.FundingNational Institutes of Health.Copyright © 2020 Elsevier Ltd. All rights reserved.

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