Safety and Immunogenicity of a 2-Dose Heterologous Vaccine Regimen With Ad26.ZEBOV and MVA-BN-Filo Ebola Vaccines: 12-Month Data From a Phase 1 Randomized Clinical Trial in Nairobi, Kenya

Gaudensia Mutua, Omu Anzala, Kerstin Luhn, Cynthia Robinson, Viki Bockstal, Dickson Anumendem, Macaya Douoguih, Gaudensia Mutua, Omu Anzala, Kerstin Luhn, Cynthia Robinson, Viki Bockstal, Dickson Anumendem, Macaya Douoguih

Abstract

Background: During the 2014 West African Ebola outbreak, Ebola vaccine development was accelerated. The phase 1 VAC52150EBL1003 study was performed to investigate 2-dose heterologous vaccination with Ad26.ZEBOV and MVA-BN-Filo in an African population located in a high-altitude setting in Nairobi, Kenya.

Methods: Healthy adult volunteers were randomized to receive one of four 2-dose vaccination schedules. The first vaccination was administered at baseline (Ad26.ZEBOV or MVA-BN-Filo), followed by the second vaccination with the alternate vaccine after either 28 or 56 days. Each schedule had a placebo comparator group. The primary objective was to assess the safety and tolerability of these regimens.

Results: Seventy-two volunteers were randomized into 4 groups of 18 (15 received vaccine, and 3 received placebo). The most frequent solicited systemic adverse event was headache (frequency, 50%, 61%, and 42% per dose for MVA-BN-Filo, Ad26.ZEBOV, and placebo, respectively). The most frequent solicited local AE was injection site pain (frequency, 78%, 63%, and 33% per dose for MVA-BN-Filo, Ad26.ZEBOV, and placebo, respectively). No differences in adverse events were observed among the different vaccine regimens. High levels of binding and neutralizing anti-Ebola virus glycoprotein antibodies were induced by all regimens and sustained to day 360 after the first dose.

Conclusions: Two-dose heterologous vaccination with Ad26.ZEBOV and MVA-BN-Filo was well tolerated and highly immunogenic against Ebola virus glycoprotein.

Clinical trials registration: NCT02376426.

Keywords: Ad26.ZEBOV; Ebola vaccine; MVA-BN-Filo; heterologous 2-dose; safety and immunogenicity.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.

Figures

Figure 1.
Figure 1.
VAC52150EBL1003 study design. Ad26, Ad26.ZEBOV; MVA, MVA-BN-Filo; TCID50, 50% tissue culture infectious doses; vp, virus particle.
Figure 2.
Figure 2.
Anti–Ebola virus glycoprotein immunoglobulin G binding antibody responses (detected by enzyme-linked immunosorbent assay [ELISA]) binding antibody responses (A) and virus neutralizing antibody (VNA) responses (B) following dose 1 vaccination with Ad26.ZEBOV (Ad26) or MVA-BN-Filo (MVA) and heterologous dose 2 vaccination with MVA or Ad26 on day 29 or day 57, 21 days after dose 2. Data are geometric mean concentration (GMC), for ELISA, and geometric mean 50% inhibitory concentration (IC50), for VNA analysis. Error bars represent 95% confidence intervals. NA, not applicable.
Figure 3.
Figure 3.
Durability of anti–Ebola virus glycoprotein immunoglobulin G binding (A) and neutralizing (B) antibody responses following dose 1 vaccination with Ad26.ZEBOV (Ad26) or MVA-BN-Filo (MVA) and heterologous dose 2 vaccination with MVA or Ad26 on day 29 or day 57. Data are geometric mean values; error bars represent 95% confidence intervals. ELISA, enzyme-linked immunosorbent assay; IC50, 50% inhibitory concentration.
Figure 4.
Figure 4.
Median CD8+ T-cell responses (A) and CD4+ T-cell responses (B) following first dose vaccination with Ad26.ZEBOV (Ad26) or MVA-BN-Filo (MVA) and heterologous second dose vaccination with MVA or Ad26 on day 29 or day 57.

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