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

• Published in: The Journal of infectious diseases Vol. 220; no. 1; pp. 46 - 56
• Main 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
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 05.06.2019
• Subjects: Adolescent; Adult; Antibodies; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Antibody Formation - immunology; Clinical trials; Disease Outbreaks - prevention & control; Ebola Vaccines - adverse effects; Ebola Vaccines - immunology; Ebola virus; Ebolavirus; Ebolavirus - immunology; Female; Headache; Healthy Volunteers; Hemorrhagic Fever, Ebola - immunology; Hemorrhagic Fever, Ebola - virology; Humans; Immunization; Immunogenicity; Major and Brief Reports; Malaria; Male; Middle Aged; Tanzania; Uganda; Vaccination - adverse effects; Vaccine development; Vaccines; Vaccines, DNA; Viral Vaccines - adverse effects; Viral Vaccines - immunology; Young Adult; Uganda; Tanzania; Ad26.ZEBOV; heterologous 2-dose; MVA-BN-Filo; safety and immunogenicity; Ebola vaccine
• ISSN: 0022-1899; 1537-6613; 1537-6613
• DOI: 10.1093/infdis/jiz070

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. 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.