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

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, 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

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.

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.
Subject disposition aOne subject did not receive Ad26.ZEBOV second dose vaccination, because he met a protocol-specific criterion for contraindication to dose 2. This subject remained in the study.
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 with MVA-BN-Filo (MVA) or Ad26.ZEBOV (Ad26) and heterologous dose 2 with Ad26 or MVA on day 29 or day 57, up to 21 days post dose 2 (day 50 or 78). 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 with MVA-BN-Filo (MVA) or Ad26.ZEBOV (Ad26) and heterologous dose 2 with Ad26 or MVA 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 with MVA-BN-Filo (MVA) or Ad26.ZEBOV (Ad26) and heterologous second dose with Ad26 or MVA on day 29 or day 57. NA, not applicable.

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Source: PubMed

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