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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.
Hamer, Melinda J; Houser, Katherine V; Hofstetter, Amelia R; Ortega-Villa, Ana M; Lee, Christine; Preston, Anne; Augustine, Brooke; Andrews, Charla; Yamshchikov, Galina V; 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 N M; Hunegnaw, Ruth; Narpala, Sandeep R; Swanson, 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, Aurélie; Sullivan, Nancy J; Ake, Julie A; Ledgerwood, Julie E.
Afiliação
  • 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.
  • 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.
  • Hofstetter AR; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • 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.
  • Lee C; Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Preston A; Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Augustine B; Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Andrews C; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Yamshchikov GV; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Hickman S; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Schech S; Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Hutter JN; Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Scott PT; Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Waterman PE; Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Amare MF; Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Kioko V; Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Storme C; Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Modjarrad K; Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • McCauley MD; Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Robb ML; Henry M Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA.
  • Gaudinski MR; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Gordon IJ; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Holman LA; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Widge AT; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Strom L; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Happe M; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Cox JH; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Vazquez S; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Stanley DA; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Murray T; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Dulan CNM; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Hunegnaw R; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Narpala SR; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Swanson PA; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Basappa M; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Thillainathan J; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Padilla M; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Flach B; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • 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.
  • Trofymenko O; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Morgan P; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Coates EE; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Gall JG; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • McDermott AB; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Koup RA; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Mascola JR; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Ploquin A; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Sullivan NJ; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
  • Ake JA; Walter Reed Army Institute of Research, Silver Spring, MD, USA.
  • Ledgerwood JE; Vaccine Research Center, and Division of Clinical Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Lancet ; 401(10373): 294-302, 2023 01 28.
Article em En | MEDLINE | ID: mdl-36709074
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. 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. 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.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Adenovirus dos Símios / Marburgvirus Tipo de estudo: Clinical_trials / Prognostic_studies Limite: Adult / Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Adenovirus dos Símios / Marburgvirus Tipo de estudo: Clinical_trials / Prognostic_studies Limite: Adult / Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article