Safety and Immunogenicity of a 2-Dose Heterologous Vaccination Regimen With Ad26.ZEBOV and MVA-BN-Filo Ebola Vaccines: 12-Month Data From a Phase 1 Randomized Clinical Trial in Uganda and Tanzania. (23rd February 2019)

• Record Type: Journal Article
• Authors: Anywaine, Zacchaeus; Whitworth, Hilary; Kaleebu, Pontiano; Praygod, George; Shukarev, Georgi; Manno, Daniela; Kapiga, Saidi; Grosskurth, Heiner; Kalluvya, Samuel; Bockstal, Viki; Anumendem, Dickson; Luhn, Kerstin; Robinson, Cynthia; Douoguih, Macaya; Watson-Jones, Deborah
• Is Part Of: Journal of infectious diseases. Volume 220:Number 1(2019)
• Page Start: 46
• Page End: 56
• Publication Date: 2019-02-23
• Subjects: Ebola vaccine -- heterologous 2-dose -- Ad26.ZEBOV -- MVA-BN-Filo -- safety and immunogenicity; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiz070
• Languages: English
• ISSNs: 0022-1899

Abstract

Abstract: Background: Ebola vaccine development was accelerated in response to the 2014 Ebola virus infection outbreak. This phase 1 study (VAC52150EBL1004) assessed safety, tolerability, and immunogenicity of heterologous 2-dose Ad26.ZEBOV, MVA-BN-Filo vaccination regimens in the Lake Victoria Basin of Tanzania and Uganda in mid-level altitude, malaria-endemic settings. Methods: Healthy volunteers aged 18–50 years from Tanzania (n = 25) and Uganda (n = 47) were randomized to receive placebo or active vaccination with Ad26.ZEBOV or MVA-BN-Filo (first vaccination), followed by MVA-BN-Filo or Ad26.ZEBOV (second vaccination) dose 2, respectively, with intervals of 28 or 56 days. Results: Seventy-two adults were randomized to receive vaccine (n = 60) or placebo (n = 12). No vaccine-related serious adverse events were reported. The most frequent solicited local and systemic adverse events were injection site pain (frequency, 70%, 66%, and 42% per dose for MVA-BN-Filo, Ad26.ZEBOV, and placebo, respectively) and headache (57%, 56%, and 46%, respectively). Adverse event patterns were similar among regimens. Twenty-one days after dose 2, 100% of volunteers demonstrated binding antibody responses against Ebola virus glycoprotein, and 87%–100% demonstrated neutralizing antibody responses. Ad26.ZEBOV dose 1 vaccination induced more-robust initial binding antibody and cellular responses than MVA-BN-Filo dose 1 vaccination. Conclusions: Heterologous 2-dose vaccination with Ad26.ZEBOV and MVA-BN-Filo against Ebola virus is well tolerated and immunogenic in healthy volunteers. Clinical trials registration: NCT02376400. Abstract : This phase 1 study demonstrated that heterologous prime-boost vaccination with Ad26.ZEBOV and MVA-BN-Filo Ebola vaccines at intervals of 28 or 56 days was well tolerated and immunogenic in healthy African adult volunteers.