BACKGROUND: Zika virus (ZIKV) may cause severe congenital disease after maternal-fetal transmission. No vaccine is currently available. OBJECTIVE: To assess the safety and immunogenicity of Ad26.ZIKV.001, a prophylactic ZIKV vaccine candidate. DESIGN: Phase 1 randomized, double-blind, placebo-controlled clinical study. (ClinicalTrials.gov: NCT03356561). SETTING: United States. PARTICIPANTS: 100 healthy adult volunteers. INTERVENTION: Ad26.ZIKV.001, an adenovirus serotype26 vector encoding ZIKV M-Env, administered in 1- or 2-doseregimens of 5 × 1010 or 1 × 1011 viral particles (vp), or placebo. MEASUREMENTS: Local and systemic adverse events; neutralization titers by microneutralization assay (MN50) and T-cell responses by interferon-γ enzyme-linked immunospot and intracellular cytokine staining; and protectivity of vaccine-induced antibodies in a subset of participants through transfer in an exploratory mouse ZIKV challenge model. RESULTS: All regimens were well tolerated, with no safety concerns identified. In both 2-dose regimens, ZIKV neutralizing titers peaked 14 days after the second vaccination, with geometric mean MN50 titers (GMTs) of 1065.6 (95% CI, 494.9 to 2294.5) for 5 × 1010 vp and 956.6 (595.8 to 1535.8) for 1 × 1011 vp. Titers persisted for at least 1 year at a GMT of 68.7 (CI, 26.4-178.9) for 5 × 1010 vp and 87.0 (CI, 29.3 to 258.6) for 1 × 1011 vp. A 1-dose regimen of 1 × 1011 vp Ad26.ZIKV.001 induced seroconversion in all participants 56 days after the first vaccination (GMT, 103.4 [CI, 52.7 to 202.9]), with titers persisting for at least 1 year (GMT, 90.2 [CI, 38.4 to 212.2]). Env-specific cellular responses were induced. Protection against ZIKV challenge was observed after antibody transfer from participants into mice, and MN50 titers correlated with protection in this model. LIMITATION: The study was conducted in a nonendemic area, so it did not assess safety and immunogenicity in a flavivirus-exposed population. CONCLUSION: The safety and immunogenicity profile makes Ad26.ZIKV.001 a promising candidate for further development if the need reemerges. PRIMARY FUNDING SOURCE: Janssen Vaccines and Infectious Diseases.
RCT Entities:
BACKGROUND:Zika virus (ZIKV) may cause severe congenital disease after maternal-fetal transmission. No vaccine is currently available. OBJECTIVE: To assess the safety and immunogenicity of Ad26.ZIKV.001, a prophylactic ZIKV vaccine candidate. DESIGN: Phase 1 randomized, double-blind, placebo-controlled clinical study. (ClinicalTrials.gov: NCT03356561). SETTING: United States. PARTICIPANTS: 100 healthy adult volunteers. INTERVENTION: Ad26.ZIKV.001, an adenovirus serotype 26 vector encoding ZIKV M-Env, administered in 1- or 2-dose regimens of 5 × 1010 or 1 × 1011 viral particles (vp), or placebo. MEASUREMENTS: Local and systemic adverse events; neutralization titers by microneutralization assay (MN50) and T-cell responses by interferon-γ enzyme-linked immunospot and intracellular cytokine staining; and protectivity of vaccine-induced antibodies in a subset of participants through transfer in an exploratory mouseZIKV challenge model. RESULTS: All regimens were well tolerated, with no safety concerns identified. In both 2-dose regimens, ZIKV neutralizing titers peaked 14 days after the second vaccination, with geometric mean MN50 titers (GMTs) of 1065.6 (95% CI, 494.9 to 2294.5) for 5 × 1010 vp and 956.6 (595.8 to 1535.8) for 1 × 1011 vp. Titers persisted for at least 1 year at a GMT of 68.7 (CI, 26.4-178.9) for 5 × 1010 vp and 87.0 (CI, 29.3 to 258.6) for 1 × 1011 vp. A 1-dose regimen of 1 × 1011 vp Ad26.ZIKV.001 induced seroconversion in all participants 56 days after the first vaccination (GMT, 103.4 [CI, 52.7 to 202.9]), with titers persisting for at least 1 year (GMT, 90.2 [CI, 38.4 to 212.2]). Env-specific cellular responses were induced. Protection against ZIKV challenge was observed after antibody transfer from participants into mice, and MN50 titers correlated with protection in this model. LIMITATION: The study was conducted in a nonendemic area, so it did not assess safety and immunogenicity in a flavivirus-exposed population. CONCLUSION: The safety and immunogenicity profile makes Ad26.ZIKV.001 a promising candidate for further development if the need reemerges. PRIMARY FUNDING SOURCE: Janssen Vaccines and Infectious Diseases.
Authors: Laura Solforosi; Harmjan Kuipers; Mandy Jongeneelen; Sietske K Rosendahl Huber; Joan E M van der Lubbe; Liesbeth Dekking; Dominika N Czapska-Casey; Ana Izquierdo Gil; Miranda R M Baert; Joke Drijver; Joost Vaneman; Ella van Huizen; Ying Choi; Jessica Vreugdenhil; Sanne Kroos; Adriaan H de Wilde; Eleni Kourkouta; Jerome Custers; Remko van der Vlugt; Daniel Veldman; Jeroen Huizingh; Krisztian Kaszas; Tim J Dalebout; Sebenzile K Myeni; Marjolein Kikkert; Eric J Snijder; Dan H Barouch; Kinga P Böszörményi; Marieke A Stammes; Ivanela Kondova; Ernst J Verschoor; Babs E Verstrepen; Gerrit Koopman; Petra Mooij; Willy M J M Bogers; Marjolein van Heerden; Leacky Muchene; Jeroen T B M Tolboom; Ramon Roozendaal; Boerries Brandenburg; Hanneke Schuitemaker; Frank Wegmann; Roland C Zahn Journal: J Exp Med Date: 2021-07-05 Impact factor: 14.307
Authors: Jerald Sadoff; Glenda Gray; An Vandebosch; Vicky Cárdenas; Georgi Shukarev; Beatriz Grinsztejn; Paul A Goepfert; Carla Truyers; Hein Fennema; Bart Spiessens; Kim Offergeld; Gert Scheper; Kimberly L Taylor; Merlin L Robb; John Treanor; Dan H Barouch; Jeffrey Stoddard; Martin F Ryser; Mary A Marovich; Kathleen M Neuzil; Lawrence Corey; Nancy Cauwenberghs; Tamzin Tanner; Karin Hardt; Javier Ruiz-Guiñazú; Mathieu Le Gars; Hanneke Schuitemaker; Johan Van Hoof; Frank Struyf; Macaya Douoguih Journal: N Engl J Med Date: 2021-04-21 Impact factor: 176.079
Authors: Lisa H Tostanoski; Abishek Chandrashekar; Shivani Patel; Jingyou Yu; Catherine Jacob-Dolan; Aiquan Chang; Olivia C Powers; Daniel Sellers; Sarah Gardner; Julia Barrett; Owen Sanborn; Kathryn E Stephenson; Jessica L Ansel; Kate Jaegle; Michael S Seaman; Maciel Porto; Megan Lok; Brittany Spence; Kathleen Cayer; Danielle Nase; Shaikim Holman; Heath Bradette; Swagata Kar; Hanne Andersen; Mark G Lewis; Freek Cox; Jeroen T B M Tolboom; Anne Marit de Groot; Dirk Heerwegh; Mathieu Le Gars; Jerald Sadoff; Frank Wegmann; Roland C Zahn; Hanneke Schuitemaker; Dan H Barouch Journal: NPJ Vaccines Date: 2022-01-10 Impact factor: 7.344
Authors: Dan H Barouch; Kathryn E Stephenson; Jerald Sadoff; Jingyou Yu; Aiquan Chang; Makda Gebre; Katherine McMahan; Jinyan Liu; Abishek Chandrashekar; Shivani Patel; Mathieu Le Gars; Anne Marit de Groot; Dirk Heerwegh; Frank Struyf; Macaya Douoguih; Johan van Hoof; Hanneke Schuitemaker Journal: medRxiv Date: 2021-07-07