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.

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.

• Authors: Zacchaeus Anywaine, Hilary Whitworth, Pontiano Kaleebu, George Praygod, Georgi Shukarev, Daniela Manno, Saidi Kapiga, Heiner Grosskurth, Samuel Kalluvya, Viki Bockstal, Dickson Anumendem, Kerstin Luhn, Cynthia Robinson, Macaya Douoguih, Deborah Watson-Jones
• Journal: The Journal of infectious diseases (J Infect Dis) Vol. 220 Issue 1 Pg. 46-56 (06 05 2019) ISSN: 1537-6613 [Electronic] United States
• PMID: 30796818 (Publication Type: Clinical Trial, Phase I, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.

Chemical References

• Antibodies, Neutralizing
• Antibodies, Viral
• Ebola Vaccines
• MVA vaccine
• Vaccines, DNA
• Viral Vaccines

Topics

• Adolescent
• Adult
• Antibodies, Neutralizing (immunology)
• Antibodies, Viral (immunology)
• Antibody Formation (immunology)
• Disease Outbreaks (prevention & control)
• Ebola Vaccines (adverse effects, immunology)
• Ebolavirus (immunology)
• Female
• Healthy Volunteers
• Hemorrhagic Fever, Ebola (immunology, virology)
• Humans
• Male
• Middle Aged
• Tanzania
• Uganda
• Vaccination (adverse effects)
• Vaccines, DNA
• Viral Vaccines (adverse effects, immunology)
• Young Adult